Anti-angiogenesis in regenerative medicine -
When CDC-Exo were injected into the infarct border zone after AMI, the scar was reduced and necrotic myocardium was repaired with neovascularization. This effect of CDC-Exo was confirmed by Gallet et al. who observed a higher number of arterioles in both infarct and border zones of exosomes derived from CDCs CDC-Exo -treated pigs [ 94 ].
Further study demonstrated that the function of CDC-Exo in neovascularization of ischemic myocardium was related to the high content of miRa. Experiments in vitro also showed that CDC-Exo increased HUVEC tube formation and promoted angiogenesis [ 95 ]. In addition, the contents of CDC-Exo can be changed under given conditions.
For example, exosomes isolated from CDCs cultured under hypoxia were enriched with proangiogenic miRNAs such as miR, miRa, and miR, which increased tube formation of HUVECs [ 96 ].
For treatment of ischemic heart disease, CDCs which are derived from myocardial tissue have lower immune responses compared with other stem cells. Furthermore, allogeneic CDC-Exo did not induce significant immune responses after repeated dosing [ ]. As a treatment for ischemia, EVs play an important role as key transporters of paracrine factors during angiogenesis [ ].
For example, scientists observed that BM-MSC-EVs can be internalized by endothelial cells and enhanced HUVEC tube formation. Moreover, fluorescence micrographs showed a large number of functional tubes forming in regions surrounding infarction areas.
Subsequent in vivo experiments observed increased blood vessel density in hearts injected with BM-MSC-EVs [ 97 ]. To determine the angiogenic effect of BM-MSC-Exo in vivo, exosomes were added to the Matrigel plug and then implanted subcutaneously.
The results suggested the enhancement of the influx of vascular cells and the blood vessel formation in the Matrigel plug. Analysis of proangiogenic factors revealed the level of extracellular matrix metalloproteinase inducer EMMPRIN was high in BM-MSC-Exo.
Knockdown of EMMPRIN leads to, both in vitro and in vivo, a diminished proangiogenic effect [ 99 ]. The exosomes were isolated from UC-MSC. In vitro, UC-MSC-Exo could promote migration of endothelial cells and tube formation, which might be associated with the increased expression of Bcl-2 family [ ].
Kang et al. observed that MVs from ADSCs, especially from endothelial differentiation medium-preconditioned ADSCs, also enhanced angiogenesis both in vitro and in vivo, but the molecular mechanism was different.
The level of miR was found to be upregulated in preconditioned ADSCs. Further study showed miR targeted factor-inhibiting hypoxia-inducible factor 1 FIH1 in vascular endothelial cells to mediate the proangiogenic effect of MVs [ ]. Another research assessed therapeutic properties of BM-MSCs, ADSCs, and endometrium-derived mesenchymal stem cells EnMSCs in a rat model of AMI and found that EnMSCs supported enhanced microvessel density.
ESCs have the ability to produce exosomes which are capable of instigating cell analogous response in target cells. In order to assess the therapeutic efficacy of ESC-derived exosome ESC-Exo in post-infarct myocardium, ESC-Exo were intramyocardially injected in mice at the time of AMI.
After 4 weeks, immunohistochemical analysis showed the capillary density was remarkably increased in ESC-Exo transplanted hearts, but the underlying basis for the effect is unknown [ ]. In recent years, iPSC researches have offered exciting opportunities for tissue restoration.
Scientists compared the angiogenesis ability of iPSCs with that of iPSC-EVs in heart failure. The results demonstrated that both iPSCs and iPSC-EVs significantly promoted the migration and tube formation of murine cardiac endothelial cells CECs. Further experimental analysis of capillary density in vivo was performed in the infarct zone, border zone, and non-ischemic zone of infarcted mouse hearts respectively.
IPSC-EV injection resulted in greater number of capillaries in the infarct zone compared with iPSC injection [ ]. Another study observed the EVs from cardiovascular progenitor cells derived from iPSCs iPSC-CPC-EVs promoted the migration and tube formation of HUVECs.
Moreover, iPSC-CPC-EVs could significantly improve chronic heart failure through decreasing left ventricular volumes and increasing left ventricular ejection fraction [ ]. Sahoo et al. Ischemia and hypoxia cause neuronal degeneration and necrosis, leading to irreversible damage in the ischemic core region [ ].
Current effective therapies include the use of tissue plasminogen activator thrombolysis and intravascular thrombectomy. However, the time window for application of these treatments is only a few hours [ ].
Moreover, most patients suffer from a certain degree of neurological dysfunction even after receiving effective thrombolytic therapy. Therefore, how to reduce ischemic injury and promote the recovery of nerve function in ischemic areas has become a research hotspot.
In recent years, a deeper understating of EVs has confirmed that the intercellular information exchange process regulated by EVs is widely involved in angiogenic processes of the cerebrovascular system [ ] Table 4.
MSCs isolated from various tissues can promote angiogenesis not only in wound healing, but also in stoke [ ]. In trying to understand the exact molecular mechanism by which different sources of MSCs exert protective roles in ischemic stroke, many studies have investigated the proangiogenesis ability of EVs.
BM-MSC-Exos were used to treat middle cerebral artery occlusion of adult male Wistar rats. The results demonstrated that endothelial cell proliferation, compared with the PBS-treated control group, was significantly increased and new capillary network was formed, suggesting that BM-MSC-Exos promote angiogenesis post stroke [ 12 , ].
Another research also found that ADSC-Exos which contained miRNAb-5p could enhance the tube length of brain microvascular endothelial cells BMECs after oxygen-glucose deprivation in vitro [ ].
Direct targets of miRb-5p were further confirmed. Yang et al. found that the mRNA and protein levels of transient receptor potential melastatin 7 TRPM7 were declined, and meanwhile, HIF-1α and VEGF were upregulated in BMECs after being cultured with b-Exos.
These researches suggest that exosomes from stem cells may represent a novel therapeutic approach for stroke recovery. Peripheral arterial obstructive disease, caused by atherosclerotic occlusion of the leg arteries, is often accompanied by moderate to severe ischemic pain in limbs, which directly affects the quality of life of patients and imposes a huge economic burden on society and families [ ].
Many researches have shown that stem cells such as MSCs and EPCs contribute to angiogenesis after hindlimb ischemia and EVs have been emerging as an important paracrine regulator for stem cells to exert positive therapeutic effects.
iPSC-derived mesenchymal stem cells iMSCs own powerful therapeutic effects through a paracrine mechanism. reported that exosomes derived from iMSCs iMSCs-Exo have the ability to promote angiogenesis after transplantation into ischemic limbs of mice [ ].
In another study, exosomes were isolated from human PMSCs cultured with a nitric oxide releasing polymer and revealed superior angiogenic effects on hind limb ischemia in a murine model.
Further analysis indicated that enhanced VEGF and miR expressions in exosomes were responsible for exosome promoting angiogenic processes [ ]. MVs derived from EPC also contained miR and miR which are known to be angiogenetic, suggesting a role of RNAs transferred by MVs in EPC-derived MVs treatment of severe hindlimb ischemia of mice [ ].
MiRp suppresses the expression of SPRED1 and simultaneously regulates the expression of genes which are involved in angiogenic pathways to promote angiogenesis [ ]. In addition, administration of BM-MSC-EVs enhanced the formation of new blood vessels in the ischemic limb. The research on mechanisms revealed the enriched presence of miRp and VEGF protein in BM-MSC-EV and the high levels of VEGFR1 and VEGFR2 in endothelial cells [ ].
The miRp induces expression of several proangiogenic mRNAs VEGF and VEGFR2 [ ]. Therefore, all above researches indicate that angiogenesis-related miRNAs and proteins are the main components in EVs to exert their proangiogenesis function.
Skin flap transplantation is the most widely used treatment in orthopedic surgery and the most effective treatment for ischemic tissue damage. Adequate blood supply is the basis for improving the survival rate of transplanted flaps. Skin flap transplantation has certain limitations in specific clinical applications, as ischemic necrosis occurs at the distal end of the flap [ ].
How to safely and effectively improve the survival rate of transplant flaps and ensure their blood supply has always been a difficult problem for burn orthopedics. Therefore, promoting the angiogenesis of flap grafts is key to solving this problem. With a flap ischemia-reperfusion injury IRI model, the capability of ADSCs to protect tissue against IRI were examined.
Treatment with ADSCs remarkably increased flap survival when compared with the control group and enhanced expression of proangiogenic genes [ ].
Further study demonstrated that ADSC-CM and ADSC-Exo increased tube formation after injection into the flaps and interleukin 6 IL-6 contained in ADSC-Exo stimulated angiogenesis and led to recovery after IRI [ ].
A specific micro-environment can be used for in vitro ADSC culture to develop the customized EVs. Compared with ADSC-Exo and control groups, exosomes isolated from ADSC exposed to low concentration of H 2 O 2 generated more cord-like structures on Matrigel in vitro and increased blood perfusion and microvascular density in the flap in vivo [ ].
These results suggest that low H 2 O 2 micro-environment facilitates the customized exosome development for cell-free therapeutic applications during skin flap transplantation. EVs have opened a new promising avenue for the treatment of ischemic diseases. Angiogenesis-related miRNAs and proteins in EVs derived from MSCs Fig.
Based on recent researches, many miRNAs including miRNAp, miRNA, miRNAa, miRNA, miRNAa, miRNA, miRNAa, miRNAp, miRNA, and miRNA are found to promote angiogenesis in ischemic disease [ 57 , 93 , 95 , , , , , , , , , , ]. VEGF, as a major mediator of angiogenesis, is the most common functional protein component in EVs [ ].
In view of the complex components in EVs, other specific functional proteins and miRNAs that play an important role in angiogenesis need to be further identified. The mechanisms of angiogenesis induced by MSC-derived EVs in ischemic diseases.
EVs from BM-MSCs, ADSCs, UC-MSCs, and PMSCs play an important role in neovascularization of ischemic diseases. MSC-derived EVs are enriched with specific cargo molecules including proteins pSTAT3, IL-6, Wnt 3a, Wnt 4, and CXCR4 and miRNAs miRNA, miRNAa, miRNAb, miRNA, miRNA, and miRNA These proteins and miRNAs activate their related signal pathway to regulate the expression of angiogenic factors in endothelial cells.
Abbreviation: IL-6, interleukin-6; FIH1, hypoxia-inducible factor 1-alpha inhibitor; HIF-1α, hypoxia-inducible factor-1α; VEGF, vascular endothelial growth factor; PTEN, phosphatase and tensin homolog. EPC-derived EVs promote angiogenesis through upregulating the expression of related transcription factors.
CDC-derived EVs are enriched with miR, miR, and miRa, which promote the expression of angiogenic proteins in endothelial cells. Abbreviation: PDGF, platelet-derived growth factor subunit; ANG-1, angiopoietin-1; VEGFA, vascular endothelial growth factor A; VEGF, vascular endothelial growth factor; bFGF, basic fibroblast growth factor; HIF-1α, hypoxia-inducible factor-1α.
EVs produced by stem cells would be expected to have many advantages in the ischemic environment. First of all, EVs could transfer signals more effectively to target cells because their lipid bilayer shell can avert proteolytic degradation.
Scientists are trying to harness the natural ability of EVs to transfer therapeutic payloads into the desired cells.
For example, siRNA was effectively delivered by plasma exosomes into the target cells, leading to selective gene silencing of MAPK-1 [ ]. Secondly, EVs contain many potential regulatory components such as miRNAs, mRNAs, and proteins. These informational molecules could function simultaneously to generate a strong effect on the characteristics of recipient cells.
MiRp and VEGF protein, as the effective components of BM-MSC-EV, have the same function to promote new blood vessel formation of endothelial cells [ ]. Finally, EVs can be applied to personalized medicine [ , ]. Gene editing in stem cells can produce the desired EVs with specific cell-surface molecules.
EVs from gene-edited patient-specific stem cells will hold potential for treatment of ischemic diseases of each individual patient. Furthermore, EVs from iPSC-derivatives can be used for an autologous therapy by activating endogenous repair. We believe that EVs generated from patient-specific iPSC-derivatives probably have a higher angiogenic effect and provide a safer way than stem cell transplantation because EVs used as cell-free therapy are not affected by the ischemic and hypoxic micro-environment and have no tumorigenic risk.
Numerous attempts to treat ischemic diseases with EVs have been made and the results are quite encouraging.
However, there are many limitations remaining to be solved. Firstly, EVs transplanted into the damaged tissues may have only short-term effects owing to their short half-life and rapid clearance by the innate immune system.
Takahashi et al. So how to maintain the retention and stability of EVs over time in vivo is a main challenge in clinical application.
demonstrated that chitosan hydrogel remarkably increased the retention of exosomes in vivo and enhanced the stability of miRNAs and proteins in exosomes, enhancing angiogenesis in ischemic site [ ].
Secondly, the efficiency of EV uptake needs to be improved. Cellular uptake of large number of EVs by target cells may improve the effects of angiogenesis. The efficiency of EVs uptake has been found to be related to intracellular and micro-environmental acidity [ ].
Finally, the administration routes of EVs must be appropriately selected. Some studies explored whether the angiogenesis effects of EVs are influenced by intravascular injection or local injection of ischemic tissue.
Results showed that topical injection of EVs made a better therapeutic effect, while intravascular injection caused EVs to degrade rapidly [ ]. In conclusion, we believe that through continued and collaborative efforts, EV-based therapy will yield satisfactory responses in patients with ischemic diseases.
Pande RL, et al. A pooled analysis of the durability and predictors of treatment response of cilostazol in patients with intermittent claudication.
Vasc Med. Article PubMed PubMed Central Google Scholar. Mellière D, et al. The underestimated advantages of iliofemoral endarterectomy. Ann Vasc Surg. Article PubMed Google Scholar. Trams EG, et al. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles.
Biochim Biophys Acta. Article CAS PubMed Google Scholar. Wu R, et al. Drug-eluting balloon versus standard percutaneous transluminal angioplasty in infrapopliteal arterial disease: a meta-analysis of randomized trials.
Int J Surg. Li S, et al. Advances in the treatment of ischemic diseases by mesenchymal stem cells. Stem Cells Int. Article CAS PubMed PubMed Central Google Scholar.
Choi M, et al. Int J Biochem Cell Biol. Fouraschen SM, et al. Secreted factors of human liver-derived mesenchymal stem cells promote liver regeneration early after partial hepatectomy.
Stem Cells Dev. Ionescu L, et al. Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action. Am J Physiol Lung Cell Mol Physiol. Panfoli I, et al. Microvesicles as promising biological tools for diagnosis and therapy.
Expert Rev Proteomics. Muralidharan-Chari V, et al. Microvesicles: mediators of extracellular communication during cancer progression. J Cell Sci. Amini A, et al.
Stereological and molecular studies on the combined effects of T photobiomodulation and human bone marrow mesenchymal stem cell conditioned medium on wound healing in diabetic rats.
J Photochem Photobiol B. Doeppner TR, et al. Extracellular vesicles improve post-stroke neuroregeneration and prevent postischemic immunosuppression.
Stem Cells Transl Med. Riazifar M, et al. Stem cell extracellular vesicles: extended messages of regeneration. Annu Rev Pharmacol Toxicol. Article CAS Google Scholar. Johnstone RM, et al.
Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles exosomes. J Biol Chem. CAS PubMed Google Scholar. Théry C, et al. Isolation and characterization of exosomes from cell culture supernatants and biological fluids.
Curr Protoc Cell Biol. Article Google Scholar. Qin J, Xu Q. Functions and application of exosomes. Acta Pol Pharm. PubMed Google Scholar.
Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. Akers JC, et al. Biogenesis of extracellular vesicles EV : exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies.
J Neuro-Oncol. Atkin-Smith GK, et al. A novel mechanism of generating extracellular vesicles during apoptosis via a beads-on-a-string membrane structure. Nat Commun. Ferguson TA, et al. J Immunol. Poon IK, et al. Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol.
Hochreiter-Hufford A, Ravichandran K. Clearing the dead: apoptotic cell sensing, recognition, engulfment, and digestion. Cold Spring Harb Perspect Biol. Choi DS, et al. Proteomics, transcriptomics and lipidomics of exosomes and ectosomes.
Proteomics of extracellular vesicles: exosomes and ectosomes. Mass Spectrom Rev. Tauro BJ, et al. Two distinct populations of exosomes are released from LIM colon carcinoma cell-derived organoids. Mol Cell Proteomics. Proteomic analysis of microvesicles derived from human colorectal cancer cells.
J Proteome Res. Safdar A, et al. The potential of endurance exercise-derived exosomes to treat metabolic diseases. Nat Rev Endocrinol. Record M, et al. Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies.
Shahabipour F, et al. Exosomes as nanocarriers for siRNA delivery: paradigms and challenges. Arch Med Sci. Hannafon BN, Ding WQ. Intercellular communication by exosome-derived microRNAs in cancer. Int J Mol Sci.
Ratajczak J, et al. Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Guescini M, et al. Astrocytes and glioblastoma cells release exosomes carrying mtDNA. J Neural Transm Vienna. Valadi H, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.
Nat Cell Biol. Xiong XD, et al. Long non-coding RNAs: an emerging powerhouse in the battle between life and death of tumor cells.
Drug Resist Updat. Ha M, Kim V. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. Bellingham SA, et al. Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells.
Nucleic Acids Res. Nolte-'t Hoen EN, et al. Deep sequencing of RNA from immune cell-derived vesicles uncovers the selective incorporation of small non-coding RNA biotypes with potential regulatory functions. Ogawa Y, et al. Small RNA transcriptomes of two types of exosomes in human whole saliva determined by next generation sequencing.
Biol Pharm Bull. Gandellini P, et al. microRNAs as players and signals in the metastatic cascade: implications for the development of novel anti-metastatic therapies. Semin Cancer Biol. Tosar JP, et al. Assessment of small RNA sorting into different extracellular fractions revealed by high-throughput sequencing of breast cell lines.
Li B, et al. piRNA delivered by multiple myeloma-derived extracellular vesicles promoted tumorigenesis through re-educating endothelial cells in the tumor environment.
Rimer JM, et al. Pi F, et al. Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression. Nat Nanotechnol. Clinton A, Carter T. Chronic wound biofilms: pathogenesis and potential therapies. Lab Med. Bhate K, Williams HC. What's new in acne?
An analysis of systematic reviews published in Clin Exp Dermatol. Lefrancois T, et al. Evidence based review of literature on detriments to healing of diabetic foot ulcers. Foot Ankle Surg. Crawford JM, et al. Pathophysiology of venous ulceration.
Lusis AJ. Uccioli L, et al. Critical limb ischemia: current challenges and future prospects. Vasc Health Risk Manag. Veeravagu A, et al. National trends in burn and inhalation injury in burn patients: results of analysis of the nationwide inpatient sample database.
J Burn Care Res. Zafren K. Frostbite: prevention and initial management. High Alt Med Biol. Pazyar N, et al. Skin wound healing and phytomedicine: a review. Skin Pharmacol Physiol. Tonnesen MG, et al. Angiogenesis in wound healing.
J Investig Dermatol Symp Proc. Shabbir A, et al. Mesenchymal stem cell exosomes induce proliferation and migration of normal and chronic wound fibroblasts, and enhance angiogenesis in vitro. Stem Cell Dev. McBride JD, et al. Ren S, et al. Microvesicles from human adipose stem cells promote wound healing by optimizing cellular functions via AKT and ERK signaling pathways.
Stem Cell Res Ther. Liang X, et al. Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miRa. Xue C, et al. Exosomes derived from hypoxia-treated human adipose mesenchymal stem cells enhance angiogenesis through the PKA signaling pathway.
Hu Y, et al. Exosomes from human umbilical cord blood accelerate cutaneous wound healing through miRp-mediated promotion of angiogenesis and fibroblast function. Zhang B, et al. Komaki M, et al.
Exosomes of human placenta-derived mesenchymal stem cells stimulate angiogenesis. Kobayashi H, et al. Effects of exosomes derived from the induced pluripotent stem cells on skin wound healing. Nagoya J Med Sci. Zhang JY, et al. Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis.
J Transl Med. Li X, et al. Exosomes derived from endothelial progenitor cells attenuate vascular repair and accelerate reendothelialization by enhancing endothelial function. Human endothelial progenitor cells-derived exosomes accelerate cutaneous wound healing in diabetic rats by promoting endothelial function.
J Diabetes Complicat. O'Loughlin A, et al. Topical administration of allogeneic mesenchymal stromal cells seeded in a collagen scaffold augments wound healing and increases angiogenesis in the diabetic rabbit ulcer.
Vojtassák J, et al. Autologous biograft and mesenchymal stem cells in treatment of the diabetic foot. Neuro Endocrinol Lett.
Shen L, et al. Neurotrophin-3 accelerates wound healing in diabetic mice by promoting a paracrine response in mesenchymal stem cells. Cell Transplant. Kim CH, et al. Mesenchymal stem cells improve wound healing in vivo via early activation of matrix metalloproteinase-9 and vascular endothelial growth factor.
J Korean Med Sci. Chen L, et al. Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS One. Choudhery MS, et al. Comparison of human mesenchymal stem cells derived from dental pulp, bone marrow, adipose tissue, and umbilical cord tissue by gene expression.
Kim SM, et al. The effect of diabetes on the wound healing potential of adipose-tissue derived stem cells. Int Wound J. Cramer C, et al. Persistent high glucose concentrations alter the regenerative potential of mesenchymal stem cells. Kim EK, et al. The effect of human adipose-derived stem cells on healing of ischemic wounds in a diabetic nude mouse model.
Plast Reconstr Surg. Kensler TW, et al. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Spirli C, et al. Ballen KK, et al. Umbilical cord blood transplantation: the first 25 years and beyond. Doi H, et al. Potency of umbilical cord blood- and Wharton's jelly-derived mesenchymal stem cells for scarless wound healing.
Sci Rep. Lee C, et al. Human umbilical cord blood-derived mesenchymal stromal cells and small intestinal submucosa hydrogel composite promotes combined radiation-wound healing of mice. Kong P, et al. Placenta mesenchymal stem cell accelerates wound healing by enhancing angiogenesis in diabetic Goto-Kakizaki GK rats.
Biochem Biophys Res Commun. Liu L, et al. Human umbilical cord mesenchymal stem cells transplantation promotes cutaneous wound healing of severe burned rats. Wang S, et al. Wound dressing model of human umbilical cord mesenchymal stem cells-alginates complex promotes skin wound healing by paracrine signaling.
Liu Z, et al. Human umbilical cord mesenchymal stem cells improve irradiation-induced skin ulcers healing of rat models. Biomed Pharmacother. Kashpur O, et al. Differentiation of diabetic foot ulcer-derived induced pluripotent stem cells reveals distinct cellular and tissue phenotypes.
FASEB J. Martin PE, et al. The potential of human induced pluripotent stem cells for modelling diabetic wound healing in vitro. Clin Sci Lond. Kanzler I, et al. Differential roles of angiogenic chemokines in endothelial progenitor cell-induced angiogenesis.
Basic Res Cardiol. Basile DP, Yoder MC. Circulating and tissue resident endothelial progenitor cells. J Cell Physiol. Zhang J, et al. Int J Biol Sci. Ertl G, Frantz S. Healing after myocardial infarction. Cardiovasc Res. Kanashiro-Takeuchi RM, et al.
Pharmacologic and genetic strategies to enhance cell therapy for cardiac regeneration. J Mol Cell Cardiol. Iglesias-García O, et al. Induced pluripotent stem cells as a new strategy for cardiac regeneration and disease modeling.
Makridakis M, et al. Stem cells: insights into the secretome. Ibrahim AG, et al. Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem Cell Reports. Lang JK, et al. Inhibiting extracellular vesicle release from human cardiosphere derived cells with lentiviral knockdown of nSMase2 differentially effects proliferation and apoptosis in cardiomyocytes, fibroblasts and endothelial cells in vitro.
Namazi H, et al. Exosomes secreted by hypoxic cardiosphere-derived cells enhance tube formation and increase pro-angiogenic miRNA. J Cell Biochem. Gallet R, et al. Exosomes secreted by cardiosphere-derived cells reduce scarring, attenuate adverse remodelling, and improve function in acute and chronic porcine myocardial infarction.
Eur Heart J. Teng XM, et al. Mesenchymal stem cell-derived exosomes improve the microenvironment of infarcted myocardium contributing to angiogenesis and anti-inflammation.
Cell Physiol Biochem. Kang K, et al. Exosomes secreted from CXCR4 overexpressing mesenchymal stem cells promote cardioprotection via Akt signaling pathway following myocardial infarction. Vrijsen KR, et al. Exosomes from cardiomyocyte progenitor cells and mesenchymal stem cells stimulate angiogenesis via EMMPRIN.
Adv Healthc Mater. Zhao YY, et al. Exosomes derived from human umbilical cord mesenchymal stem cells relieve acute myocardial ischemic injury. Kang T, et al. Adipose-derived stem cells induce angiogenesis via microvesicle transport of miRNA Wang K, et al.
Enhanced cardioprotection by human endometrium mesenchymal stem cells driven by exosomal microRNA Khan M, et al. Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction.
Circ Res. Adamiak M, et al. Induced pluripotent stem cell iPSC -derived extracellular vesiclesare safer and more effective for cardiac repair than iPSCs. El Harane N, et al. Acellular therapeutic approach for heart failure: in vitro production of extracellular vesicles from human cardiovascular progenitors.
Sahoo S, et al. Marbán E. Breakthroughs in cell therapy for heart disease: focus on cardiosphere-derived cells. Mayo Clin Proc. Smith RR, et al. Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens.
Kreke M, et al. Cardiospheres and cardiosphere-derived cells as therapeutic agents following myocardial infarction. Expert Rev Cardiovasc Ther. Mirotsou M, et al. The expression of VEGFR-2, as a tyrosine kinase-related receptors, was also induced as well [ ]. The use of suitable scaffolds with appropriate physicochemical stability and combination with various factors and ECM components could re-organize cells alignment in the favor of vascularization and engineered vascular grafts.
In accordance with a great body of previous studies and what is highlighted in the current review article, angiogenesis is the main target and reliable mean to increase the efficiency of tissue regeneration by cell transplantation, gene therapy, and factor release.
Based on target tissues, inherent advantages and limitations of each delivery method must be considered. Choosing distinct cell type, selection of scaffolds and carriers fabricated by different biomaterials, and orientation of cells to vascular cells using growth factors and genetic manipulation seem pivotal to accelerate the vascularization rate.
It seems that different scaffolds could influence the rate of angiogenesis via regulating cell morphology and alignment inside the matrices. In some cases, cell-free strategies could also eliminate the need for simultaneous application of cells with growth factors. As a matter of fact, application and invention of novel strategies with the capability to preserve factors for long periods with a sustained release activity must be at the center of attention.
Exosomes, as cell byproducts encompassing a large number of factors, having a high stability could be introduced as angiogenic bio-shuttles with various scaffolds without any unpredictable complications.
In addition to the composition and structure of scaffolds, the bioavailability, biodegradability, and route of administration must be detected related to distinct tissue type.
Rana D, Zreiqat H, Benkirane-Jessel N, Ramakrishna S, Ramalingam M. Development of decellularized scaffolds for stem cell-driven tissue engineering. J Tissue Eng Regen Med. Article Google Scholar. Cosson S, Otte EA, Hezaveh H, Cooper-White JJ.
Concise review: tailoring bioengineered scaffolds for stem cell applications in tissue engineering and regenerative medicine. Stem Cells Transl Med. Rezaie J, Mehranjani MS, Rahbarghazi R, Shariatzadeh MA. Angiogenic and Restorative Abilities of Human Mesenchymal Stem Cells Were Reduced Following Treatment With Serum From Diabetes Mellitus Type 2 Patients.
J Cell Biochem. Hassanpour M, Cheraghi O, Siavashi V, Rahbarghazi R, Nouri M. A reversal of age-dependent proliferative capacity of endothelial progenitor cells from different species origin in in vitro condition. J Cardiovasc Thor Res. Mueller SB, Kontos CD.
J Clin Invest. Song H, Cheng Y, Bi G, Zhu Y, Jun W, Ma W, et al. Release of matrix Metalloproteinases-2 and 9 by S-Nitrosylated Caveolin-1 contributes to degradation of extracellular matrix in tPA-treated hypoxic endothelial cells.
PLoS One. Rohlenova K, Veys K, Miranda-Santos I, De Bock K, Carmeliet P. Endothelial cell metabolism in health and. Trends Cell Biol. Díaz-Flores L, Gutiérrez R, González-Gómez M, García P, Sáez FJ, Díaz-Flores L Jr, et al. Segmentation of dilated Hemorrhoidal veins in Hemorrhoidal disease.
Cells Tissues Organs. Paku S, Dezső K, Bugyik E, Tóvári J, Tímár J, Nagy P, et al. A new mechanism for pillar formation during tumor-induced intussusceptive angiogenesis: inverse sprouting. Am J Pathol. Lancerotto L, Orgill DP. Mechanoregulation of angiogenesis in wound healing. Adv Wound Care.
Kumar G, Narayan B. The biology of fracture healing in long bones. Classic Papers in Orthopaedics. Springer; Madeddu P.
Therapeutic angiogenesis and vasculogenesis for tissue regeneration. Exp Physiol. Bjelakovic MD, Vlajkovic S, Petrovic A, Bjelakovic M, Antic M.
Stereological study of developing glomerular forms during human fetal kidney development. Pediatr Nephrol. Selvam S, Kumar T, Fruttiger M. Retinal vasculature development in health and disease. Prog Retin Eye Res. MCAK-mediated regulation of endothelial cell microtubule dynamics is mechanosensitive to myosin-II contractility.
Mol Biol Cell. Du P, Suhaeri M, Ha SS, Oh SJ, Kim S-H, Park K. Human lung fibroblast-derived matrix facilitates vascular morphogenesis in 3D environment and enhances skin wound healing. Acta Biomater. Frismantiene A, Philippova M, Erne P, Resink TJ. Cadherins in vascular smooth muscle cell patho biology: quid nos scimus?
Cell Signal. Cheresh D, Stupack D. Regulation of angiogenesis: apoptotic cues from the ECM. Hoenig MR, Campbell GR, Rolfe BE, Campbell JH. Tissue-engineered blood vessels: alternative to autologous grafts?
Arterioscler Thromb Vasc Biol. Dean EW, Udelsman B, Breuer CK. Current advances in the translation of vascular tissue engineering to the treatment of pediatric congenital heart disease.
Yale J Biol Med. Google Scholar. Dahl SL, Kypson AP, Lawson JH, Blum JL, Strader JT, Li Y, et al. Readily available tissue-engineered vascular grafts. Sci Transl Med. Nemeno-Guanzon JG, Lee S, Berg JR, Jo YH, Yeo JE, Nam BM, et al.
Trends in tissue engineering for blood vessels. Biomed Res Int. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Jung YJ, Kim K-C, Heo J-Y, Jing K, Lee KE, Hwang JS, et al. Mol Cells. Sun X, Altalhi W, Nunes SS. Vascularization strategies of engineered tissues and their application in cardiac regeneration.
Adv Drug Deliv Rev. Zureikat AH, Nguyen T, Boone BA, Wijkstrom M, Hogg ME, Humar A, et al. Robotic total pancreatectomy with or without autologous islet cell transplantation: replication of an open technique through a minimal access approach.
Surg Endosc. Ong CS, Zhou X, Huang CY, Fukunishi T, Zhang H, Hibino N. Tissue engineered vascular grafts: current state of the field.
Expert Rev Med Devices. Pinho SS, Reis CA. Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer. Khademhosseini A, Langer R. A decade of progress in tissue engineering. Nat Protoc. Serbo JV, Gerecht S. Vascular tissue engineering: biodegradable scaffold platforms to promote angiogenesis.
Stem Cell Res Ther. Ingram DA, Mead LE, Tanaka H, Meade V, Fenoglio A, Mortell K, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood.
Traktuev DO, Merfeld-Clauss S, Li J, Kolonin M, Arap W, Pasqualini R, et al. A population of multipotent CDpositive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. Circ Res. Tang F, Barbacioru C, Bao S, Lee C, Nordman E, Wang X, et al.
Tracing the derivation of embryonic stem cells from the inner cell mass by single-cell RNA-Seq analysis. Cell Stem Cell. Paoletti C, Divieto C, Chiono V. Impact of biomaterials on differentiation and reprogramming approaches for the generation of functional cardiomyocytes.
Lu S-J, Ivanova Y, Feng Q, Luo C, Lanza R. Hemangioblasts from human embryonic stem cells generate multilayered blood vessels with functional smooth muscle cells; Book Google Scholar.
Le Belle JE, Orozco NM, Paucar AA, Saxe JP, Mottahedeh J, Pyle AD, et al. Zhang P, Moudgill N, Hager E, Tarola N, DiMatteo C, McIlhenny S, et al.
Endothelial differentiation of adipose-derived stem cells from elderly patients with cardiovascular disease. Stem Cells Dev. Mauritz C, Schwanke K, Reppel M, Neef S, Katsirntaki K, Maier LS, et al. Generation of functional murine cardiac myocytes from induced pluripotent stem cells.
Tateishi K, Takehara N, Matsubara H, Oh H. Stemming heart failure with cardiac-or reprogrammed-stem cells. J Cell Mol Med. Stadtler H. Supply chain management: An overview. Supply chain management and advanced planning. Lee A-Y, Lee J, Kim C-L, Lee KS, Lee S-H, Gu N-Y, et al.
Comparative studies on proliferation, molecular markers and differentiation potential of mesenchymal stem cells from various tissues adipose, bone marrow, ear skin, abdominal skin, and lung and maintenance of multipotency during serial passages in miniature pig.
Res Vet Sci. Richard A, Boullu L, Herbach U, Bonnafoux A, Morin V, Vallin E, et al. Single-cell-based analysis highlights a surge in cell-to-cell molecular variability preceding irreversible commitment in a differentiation process. PLoS Biol.
Kajstura J, Urbanek K, Rota M, Bearzi C, Hosoda T, Bolli R, et al. Cardiac stem cells and myocardial disease. J Mol Cell Cardiol. Masuda S, Shimizu T. Three-dimensional cardiac tissue fabrication based on cell sheet technology.
Roura S, Soler-Botija C, Bagó JR, Llucià-Valldeperas A, Férnandez MA, Gálvez-Montón C, et al. Postinfarction functional recovery driven by a three-dimensional engineered fibrin patch composed of human umbilical cord blood-derived mesenchymal stem cells.
Avior Y, Sagi I, Benvenisty N. Pluripotent stem cells in disease modelling and drug discovery. Nat Rev Mol Cell Biol. Singh KP, Sharma AM.
Critical limb ischemia: current approach and future directions. J Cardiovasc Transl Res. Gonzales-Portillo GS, Sanberg PR, Franzblau M, Gonzales-Portillo C, Diamandis T, Staples M, et al. Mannitol-enhanced delivery of stem cells and their growth factors across the blood-brain barrier.
Cell Transplant. Zhang WJ, Liu W, Cui L, Cao Y. Tissue engineering of blood vessel. Singh S, Wu BM, Dunn JC. The enhancement of VEGF-mediated angiogenesis by polycaprolactone scaffolds with surface cross-linked heparin. Hussain A, Cahalan P, Cahalan L. Methods of making bioactive collagen medical scaffolds such as for wound care dressings, hernia repair prosthetics, and surgical incision closure members.
Google Patents; Singelyn JM, DeQuach JA, Seif-Naraghi SB, Littlefield RB, Schup-Magoffin PJ, Christman KL.
Naturally derived myocardial matrix as an injectable scaffold for cardiac tissue engineering. Mima Y, Fukumoto S, Koyama H, Okada M, Tanaka S, Shoji T, et al. Enhancement of cell-based therapeutic angiogenesis using a novel type of injectable scaffolds of hydroxyapatite-polymer nanocomposite microspheres.
Lee TC, Niederer P. Basic engineering for medics and biologists: an ESEM primer: IOS Press; Lyons FG, Al-Munajjed AA, Kieran SM, Toner ME, Murphy CM, Duffy GP, et al. The healing of bony defects by cell-free collagen-based scaffolds compared to stem cell-seeded tissue engineered constructs.
DiMuzio P, Tulenko T. Tissue engineering applications to vascular bypass graft development: the use of adipose-derived stem cells. J Vasc Surg.
Lee SJ, Liu J, Oh SH, Soker S, Atala A, Yoo JJ. Development of a composite vascular scaffolding system that withstands physiological vascular conditions. Chan B, Leong K. Scaffolding in tissue engineering: general approaches and tissue-specific considerations. Eur Spine J. Pektok E, Nottelet B, Tille J-C, Gurny R, Kalangos A, Moeller M, et al.
Degradation and healing characteristics of small-diameter poly ε-caprolactone vascular grafts in the rat systemic arterial circulation. Rocco KA, Maxfield MW, Best CA, Dean EW, Breuer CK.
In vivo applications of electrospun tissue-engineered vascular grafts: a review. Tissue Eng B Rev. Daley WP, Peters SB, Larsen M. Extracellular matrix dynamics in development and regenerative medicine.
J Cell Sci. Hutmacher DW, Schantz JT, Lam CXF, Tan KC, Lim TC. State of the art and future directions of scaffold-based bone engineering from a biomaterials perspective. Ma Z, Mao Z, Gao C. Surface modification and property analysis of biomedical polymers used for tissue engineering.
Colloids Surf B: Biointerfaces. Calabrese G, Giuffrida R, Fabbi C, Figallo E, Furno DL, Gulino R, et al. Collagen-hydroxyapatite scaffolds induce human adipose derived stem cells osteogenic differentiation in vitro. MJPd S. Development of paper-based devices, using a simple phase separation process for the fabrication of biomimetic superhydrophobic paper substrates; McKenna KA, Hinds MT, Sarao RC, Wu P-C, Maslen CL, Glanville RW, et al.
Mechanical property characterization of electrospun recombinant human tropoelastin for vascular graft biomaterials. Aper T, Schmidt A, Duchrow M, Bruch H-P.
Autologous blood vessels engineered from peripheral blood sample. Eur J Vasc Endovasc Surg. Rowe SL, Lee S, Stegemann JP. Influence of thrombin concentration on the mechanical and morphological properties of cell-seeded fibrin hydrogels.
Ye Q, Zünd G, Benedikt P, Jockenhoevel S, Hoerstrup SP, Sakyama S, et al. Fibrin gel as a three dimensional matrix in cardiovascular tissue engineering. Eur J Cardiothorac Surg. Neidert M, Lee E, Oegema T, Tranquillo R. Enhanced fibrin remodeling in vitro with TGF-β1, insulin and plasmin for improved tissue-equivalents.
Tam SK, Dusseault J, Polizu S, Ménard M, Hallé J-P, Yahia LH. Salgado CL, Oliveira MB, Mano JF. Combinatorial cell—3D biomaterials cytocompatibility screening for tissue engineering using bioinspired superhydrophobic substrates.
Integr Biol. Oliveira MB, Ribeiro MP, Miguel SP, Neto AI, Coutinho P, Correia IJ, et al. In vivo high-content evaluation of three-dimensional scaffolds biocompatibility.
Tissue Eng Part C Methods. Yu J, Gu Y, Du KT, Mihardja S, Sievers RE, Lee RJ. The effect of injected RGD modified alginate on angiogenesis and left ventricular function in a chronic rat infarct model.
Puga AM, Lima AC, Mano JF, Concheiro A, Alvarez-Lorenzo C. Pectin-coated chitosan microgels crosslinked on superhydrophobic surfaces for 5-fluorouracil encapsulation.
Carbohydr Polym. Ameres SL, Horwich MD, Hung J-H, Xu J, Ghildiyal M, Weng Z, et al. Target RNA—directed trimming and tailing of small silencing RNAs.
Lennox KA, Behlke MA. A direct comparison of anti-microRNA oligonucleotide potency. Pharm Res. Bader A, Brown D, Stoudemire J, Lammers P. Developing therapeutic microRNAs for cancer.
Gene Ther. Khalil IA, Kogure K, Akita H, Harashima H. Uptake pathways and subsequent intracellular trafficking in nonviral gene delivery. Pharmacol Rev. Zhang Y, Wang Z, Gemeinhart RA. Progress in microRNA delivery. J Control Release. Ruberti F, Barbato C, Cogoni C.
Targeting microRNAs in neurons: tools and perspectives. Exp Neurol. Fabani MM, Abreu-Goodger C, Williams D, Lyons PA, Torres AG, Smith KG, et al. Efficient inhibition of miR function in vivo by peptide nucleic acids. Nucleic Acids Res. Li Y, Fan L, Liu S, Liu W, Zhang H, Zhou T, et al.
The promotion of bone regeneration through positive regulation of angiogenic—osteogenic coupling using microRNAa. Shang J, Liu H, Zhou Y. Roles of microRNAs in prenatal chondrogenesis, postnatal chondrogenesis and cartilage-related diseases. Yang B, Guo H, Zhang Y, Chen L, Ying D, Dong S.
MicroRNA regulates chondrogenic differentiation of mesenchymal stem cells by targeting Sox9. van Rooij E, Purcell AL, Levin AA.
Developing microRNA therapeutics. Liu YP, Berkhout B. miRNA cassettes in viral vectors: problems and solutions. Biochimica et Biophysica Acta BBA -Gene Regulatory Mechanisms. Elmén J, Lindow M, Schütz S, Lawrence M, Petri A, Obad S, et al.
LNA-mediated microRNA silencing in non-human primates. Hullinger TG, Montgomery RL, Seto AG, Dickinson BA, Semus HM, Lynch JM, et al. Inhibition of miR protects against cardiac ischemic InjuryNovelty and significance. Bjørge IM, Kim SY, Mano J, Kalionis B, Chrzanowski W.
Extracellular vesicles, exosomes and shedding vesicles in regenerative medicine—a new paradigm for tissue repair. Biomaterials science. Ludwig N, Yerneni SS, Razzo BM, Whiteside TL. Exosomes from HNSCC promote angiogenesis through reprogramming of endothelial cells.
Mol Cancer Res. Liang X, Zhang L, Wang S, Han Q, Zhao RC. Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miRa. Ohyashiki JH, Umezu T, Ohyashiki K.
Exosomes promote bone marrow angiogenesis in hematologic neoplasia: the role of hypoxia. Curr Opin Hematol. Ribeiro MF, Zhu H, Millard RW, Fan G-C. Exosomes function in pro- and anti-angiogenesis. Current angiogenesis. Zhang J, Liu X, Li H, Chen C, Hu B, Niu X et al. Qi X, Zhang J, Yuan H, Xu Z, Li Q, Niu X, et al.
Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells repair critical-sized bone defects through enhanced angiogenesis and osteogenesis in osteoporotic rats.
Int J Biol Sci. Juliano RL, Ming X, Nakagawa O. Cellular uptake and intracellular trafficking of antisense and siRNA oligonucleotides.
Bioconjug Chem. Suh JS, Lee JY, Choi YS, Chong PC, Park YJ. Peptide-mediated intracellular delivery of miRNAb for osteogenic stem cell differentiation. Wu K, Song W, Zhao L, Liu M, Yan J, Andersen MØ, et al.
MicroRNA functionalized microporous titanium oxide surface by lyophilization with enhanced osteogenic activity. ACS Appl Mater Interfaces. Simón-Yarza T, Formiga FR, Tamayo E, Pelacho B, Prosper F, Blanco-Prieto MJ. Vascular endothelial growth factor-delivery systems for cardiac repair: an overview.
Heyde M, Partridge KA, Howdle SM, Oreffo RO, Garnett MC, Shakesheff KM. Development of a slow non-viral DNA release system from PDLLA scaffolds fabricated using a supercritical CO2 technique.
Biotechnol Bioeng. Subramani B, Subbannagounder S, Palanivel S, Ramanathanpullai C, Sivalingam S, Yakub A, et al.
Generation and characterization of human cardiac resident and non-resident mesenchymal stem cell. Hallmann R, Zhang X, Di Russo J, Li L, Song J, Hannocks M-J, et al.
The regulation of immune cell trafficking by the extracellular matrix. Curr Opin Cell Biol. Friedl P, Mayor R. Tuning collective cell migration by cell—cell junction regulation.
Cold Spring Harb Perspect Biol. Alcover A, Alarcón B, Di Bartolo V. Cell biology of T cell receptor expression and regulation. Annu Rev Immunol 0. Siton-Mendelson O, Bernheim-Groswasser A.
Functional actin networks under construction: the cooperative action of actin nucleation and elongation factors. Trends Biochem Sci. Mui KL, Chen CS, Assoian RK. The mechanical regulation of integrin—cadherin crosstalk organizes cells, signaling and forces. Zhang Y, Lei Z, Qi Y, Di T, Li G, Zhang W, et al.
Adipose-derived stem cell sheet encapsulated construct of micro-porous decellularized cartilage debris and hydrogel for cartilage defect repair. Med Hypotheses. Jansen PL, Rosch R, Jansen M, Binnebösel M, Junge K, Alfonso-Jaume A, et al.
Regulation of MMP-2 gene transcription in dermal wounds. J Investig Dermatol. Reymond N, d'Água BB, Ridley AJ. Crossing the endothelial barrier during metastasis.
Kitamura T, Qian B-Z, Pollard JW. Immune cell promotion of metastasis. Nat Rev Immunol. Grellier M, Bordenave L, Amedee J. Cell-to-cell communication between osteogenic and endothelial lineages: implications for tissue engineering. Trends Biotechnol. Chen G, Deng C, Li Y-P. TGF-β and BMP signaling in osteoblast differentiation and bone formation.
Li B, Xiu R. Angiogenesis: from molecular mechanisms to translational implications. Clin Hemorheol Microcirc. Aguirre A, González A, Navarro M, Castaño Linares Ó, Planell Estany JA, Engel LE. Control of microenvironmental cues with a smart biomaterial composite promotes endothelial progenitor cell angiogenesis.
European cells and materials. Bach F, Albertini R, Joo P, Anderson J, Bortin M. Bone-marrow transplantation in a patient with the Wiskott-Aldrich syndrome. Saporta S, Kim J-J, Willing AE, Fu ES, Davis CD, Sanberg PR.
Human umbilical cord blood stem cells infusion in spinal cord injury: engraftment and beneficial influence on behavior.
J Hematother Stem Cell Res. De Coppi P, Bartsch G Jr, Siddiqui MM, Xu T, Santos CC, Perin L, et al. Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol. Uygun BE, Soto-Gutierrez A, Yagi H, Izamis M-L, Guzzardi MA, Shulman C, et al.
Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med. L'heureux N, Pâquet S, Labbé R, Germain L, Auger FA. A completely biological tissue-engineered human blood vessel. FASEB J. Leeper NJ, Hunter AL, Cooke JP. Stem cell therapy for vascular regeneration: adult, embryonic, and induced pluripotent stem cells.
Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts.
Sampogna G, Guraya SY, Forgione A. Regenerative medicine: historical roots and potential strategies in modern medicine. J Microsc Ultrastruct. Atala A. Tissue engineering for the replacement of organ function in the genitourinary system.
Am J Transplant. Roubelakis MG, Pappa KI, Bitsika V, Zagoura D, Vlahou A, Papadaki HA, et al. Molecular and proteomic characterization of human mesenchymal stem cells derived from amniotic fluid: comparison to bone marrow mesenchymal stem cells.
Mirabella T, MacArthur J, Cheng D, Ozaki C, Woo Y, Yang M, et al. Nat Biomed Eng. Kim KL, Han DK, Park K, Song S-H, Kim JY, Kim J-M, et al. Enhanced dermal wound neovascularization by targeted delivery of endothelial progenitor cells using an RGD-g-PLLA scaffold. Farré-Guasch E, Bravenboer N, Helder MN, Schulten EAJM, Ten Bruggenkate CM, Klein-Nulend J.
Blood Vessel Formation and Bone Regeneration Potential of the Stromal Vascular Fraction Seeded on a Calcium Phosphate Scaffold in the Human Maxillary Sinus Floor Elevation Model. Materials Basel, Switzerland. Wang L, Shi Q, Dai J, Gu Y, Feng Y, Chen L.
Increased vascularization promotes functional recovery in the transected spinal cord rats by implanted vascular endothelial growth factor-targeting collagen scaffold. J Orthop Res. Lord MS, Ellis AL, Farrugia BL, Whitelock JM, Grenett H, Li C, et al.
Perlecan and vascular endothelial growth factor-encoding DNA-loaded chitosan scaffolds promote angiogenesis and wound healing. Teo GSL, Yang Z, Carman CV, Karp JM, Lin CP. Intravital imaging of mesenchymal stem cell trafficking and association with platelets and neutrophils. Stem Cells. Sivanathan KN, Gronthos S, Rojas-Canales D, Thierry B, Coates PT.
Interferon-gamma modification of mesenchymal stem cells: implications of autologous and allogeneic mesenchymal stem cell therapy in allotransplantation. Stem Cell Rev Rep. Kean TJ, Lin P, Caplan AI, Dennis JE.
MSCs: delivery routes and engraftment, cell-targeting strategies, and immune modulation. Stem Cells Int. Pan Q, Zheng J, Du D, Liao X, Ma C, Yang Y, et al. MicroRNA priming enhances functions of endothelial progenitor cells under physiological and hypoxic conditions and their therapeutic efficacy in cerebral ischemic damage.
Ngo VA, Jung J-Y, Koh J-T, Oh W-M, Hwang Y-C, Lee B-N. Leptin induces odontogenic differentiation and angiogenesis in human dental pulp cells via activation of the mitogen-activated protein kinase signaling pathway. J Endod. Essaadi A, Nollet M, Moyon A, Stalin J, Simoncini S, Balasse L, et al.
Stem cell properties of peripheral blood endothelial progenitors are stimulated by soluble CD via miR potential use in autologous cell therapy. Sci Rep. Bian S, Zhang L, Duan L, Wang X, Min Y, Yu H. Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model.
J Mol Med. Ibrahim AG-E, Cheng K, Marbán E. Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem Cell Rep. Feng Y, Huang W, Wani M, Yu X, Ashraf M.
Ischemic preconditioning potentiates the protective effect of stem cells through secretion of exosomes by targeting Mecp2 via miR Zhou Y, Li P, Goodwin AJ, Cook JA, Halushka PV, Chang E, et al. Exosomes from endothelial progenitor cells improve the outcome of a murine model of sepsis.
Mol Ther. Yang H, Zhang H, Ge S, Ning T, Bai M, Li J, et al. Exosome-derived miRa activates angiogenesis in gastric Cancer by targeting C-MYB in vascular endothelial cells. Zhang W, Zhang J, Cheng L, Ni H, You B, Shan Y, et al. A disintegrin and metalloprotease containing exosomes derived from nasal polyps promote angiogenesis and vascular permeability.
Mol Med Rep. Shen Y, Liu X, Huang Z, Pei N, Xu J, Li Z, et al. Comparison of magnetic intensities for mesenchymal stem cell targeting therapy on ischemic myocardial repair: high magnetic intensity improves cell retention but has no additional functional benefit.
Correlation of quantitative parameters of magnetic resonance perfusion-weighted imaging with vascular endothelial growth factor, microvessel density and hypoxia-inducible factor-1α in nasopharyngeal carcinoma: Evaluation on radiosensitivity study.
Clin Otolaryngol. Balint R, Cassidy NJ, Cartmell SH. Electrical stimulation: a novel tool for tissue engineering. Toma C, Fisher A, Wang J, Chen X, Grata M, Leeman J, et al.
Vascular endoluminal delivery of mesenchymal stem cells using acoustic radiation force. Tissue Eng A. Hanawa K, Ito K, Aizawa K, Shindo T, Nishimiya K, Hasebe Y, et al. Low-intensity pulsed ultrasound induces angiogenesis and ameliorates left ventricular dysfunction in a porcine model of chronic myocardial ischemia.
PloS One. Bhise NS, Shmueli RB, Sunshine JC, Tzeng SY, Green JJ. Drug delivery strategies for therapeutic angiogenesis and antiangiogenesis. Expert Opin Drug Deliv. Park H-J, Jin Y, Shin J, Yang K, Lee C, Yang HS, et al.
Catechol-functionalized hyaluronic acid hydrogels enhance angiogenesis and osteogenesis of human adipose-derived stem cells in critical tissue defects. Health NIo. Estimates of funding for various research, condition, and disease categories RCDC.
Choi C, Kim HM, Shon J, Park J, Kim H-T, Kang SH, et al. The combination of mannitol and temozolomide increases the effectiveness of stem cell treatment in a chronic stroke model.
Mannitol-enhanced delivery of stem cells and their growth factors across the blood—brain barrier. Pachence JM. Collagen-based devices for soft tissue repair. J Biomed Mater Res A. Xia X, Li J, Xia B, Yang H, Zhang D, Zhou B, et al. Matrigel scaffold combined with ad-hBMP7-transfected chondrocytes improves the repair of rabbit cartilage defect.
Exp Ther Med. Costa NL, Sher P, Mano JF. Liquefied capsules coated with multilayered polyelectrolyte films for cell immobilization.
Adv Eng Mater. Costa RR, Testera AM, Arias FJ, Rodríguez-Cabello JC, Mano JF. Layer-by-layer film growth using polysaccharides and recombinant polypeptides: a combinatorial approach. J Phys Chem B. Tsai M-C, Hung K-C, Hung S-C, S-h H. Evaluation of biodegradable elastic scaffolds made of anionic polyurethane for cartilage tissue engineering.
Tan H, Chu CR, Payne KA, Marra KG. Injectable in situ forming biodegradable chitosan—hyaluronic acid based hydrogels for cartilage tissue engineering. Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A, et al. MicroRNAa controls angiogenesis and functional recovery of ischemic tissues in mice.
Kalinina N, Klink G, Glukhanyuk E, Lopatina T, Efimenko A, Akopyan Z, et al. miRa regulates angiogenic activity of adipose-derived mesenchymal stromal cells.
Exp Cell Res. Liu Y, Luo F, Wang B, Li H, Xu Y, Liu X, et al. STAT3-regulated exosomal miR promotes angiogenesis and is involved in neoplastic processes of transformed human bronchial epithelial cells.
Cancer Lett. Mao G, Liu Y, Fang X, Liu Y, Fang L, Lin L, et al. Tumor-derived microRNA promotes angiogenesis in non-small cell lung cancer. Kucharzewska P, Christianson H, Welch J, Svensson K, Fredlund E.
Morgelin, E. Bourseau-Guilmain, J. Bengzon, and M. Proc Natl Acad Sci USA. Download references. Stem Cell Research Center, Tabriz University of Medical Sciences, Imam Reza St. Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
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Roberto Gianni-Barrera and Nunzia Di Maggio medjcine equally to the study. Roberto Anti-angiogeensis, Nunzia Anti-angiogenesis in regenerative medicine Maggio, Ludovic Melly, Regeberative G. Burger, Edin High cholesterol levels, Lorenz Gürke, Dirk J. Therapeutic angiogenesis, that is, the Anti-angiogenesis in regenerative medicine Anti-angiogeenesis new regensrative by delivery of specific factors, is required both for rapid vascularization of tissue-engineered constructs and to treat ischemic conditions. Vascular endothelial growth factor VEGF is the master regulator of angiogenesis. However, uncontrolled expression can lead to aberrant vascular growth and vascular tumors angiomas. Major challenges to fully exploit VEGF potency for therapy include the need to precisely control in vivo distribution of growth factor dose and duration of expression.
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