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http://dx.doi.org/10.5352/JLS.2022.32.7.567

Development of Cell Therapeutics against Ischemic Vascular Diseases Using Mesenchymal Stem Cells: From Bench to Bed  

Lee, Eun Ji (Department of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Convergence Stem Cell Research Center, Medical Research Institute, Pusan National University School of Medicine)
Park, Shin Hu (Pusan National University School of Medicine)
Seo, Jeong Ho (Pusan National University School of Medicine)
An, Hyo Gyung (Pusan National University School of Medicine)
Nam, Si Hyun (Pusan National University School of Medicine)
Kwon, Sang-Mo (Department of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Convergence Stem Cell Research Center, Medical Research Institute, Pusan National University School of Medicine)
Publication Information
Journal of Life Science / v.32, no.7, 2022 , pp. 567-577 More about this Journal
Abstract
Recently, the prevalence of ischemic diseases, such as ischemic heart disease, cerebral ischemia, and peripheral arterial disease, has been continuously increasing due to the aging population. The current standardized treatment for ischemic diseases is reperfusion therapy through pharmacotherapy and surgical approaches. Although reperfusion therapy may restore the function of damaged arteries, it is not effective at restoring the function of the surrounding tissues that have been damaged due to ischemia. Therefore, it is necessary to develop a new treatment strategy that can safely and effectively treat ischemic damage and restore the function of surrounding tissues. To overcome these limitations, stem cell-based therapy to regenerate the damaged region has been studied as a promising strategy for ischemic vascular diseases. Mesenchymal stem cells (MSCs) can be isolated from diverse tissues and have been shown to be promising for the treatment of ischemic disease by regenerating damaged tissues through immunomodulation, the promotion of angiogenesis, and the secretion of various relevant factors. Moreover, new approaches to enhancing MSC function, such as cell priming or enhancing transplantation efficiency using a 3D culture method, have been studied to increase stem cell therapeutic efficacy. In this review, we provide various strategies by which MSCs are used to treat ischemic diseases, and we discuss the challenges of MSC transplantation, such as the differentiation, proliferation, and engraftment of MSCs at the ischemic site.
Keywords
Ischemic heart disease; Ischemic stroke; Mesenchymal stem cells; Peripheral artery disease; stem cell therapy;
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1 Diez-Tejedor, E., Gutierrez-Fernandez, M., Martinez-Sanchez, P., Rodriguez-Frutos, B., Ruiz-Ares, G. and Gimeno, B. F. 2014. Reparative therapy for acute ischemic stroke with allogeneic mesenchymal stem cells from adipose tissue: a safety assessment: a phase II randomized, double-blind, placebo-controlled, single-center, pilot clinical trial. J. Stroke Cerebrovasc. Dis. 23, 2694-2700.   DOI
2 Chung, N., Jee, B. K., Chae, S. W., Jeon, Y. W., Lee, K. H. and Rha, H. K. 2009. HOX gene analysis of endothelial cell differentiation in human bone marrow-derived mesenchymal stem cells. Mol. Biol. Rep. 36, 227-235.   DOI
3 Connick, P., Kolappan, M., Crawley, C., Webber, D. J., Patani, R. and Chandran, S. 2012. Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proofof-concept study. Lancet Neurol. 11, 150-156.   DOI
4 Florea, V., Rieger, A. C., DiFede, D. L., El-Khorazaty, J., Natsumeda, M. and Hare, J. M. 2017. Dose Comparison Study of Allogeneic Mesenchymal Stem Cells in Patients With Ischemic Cardiomyopathy (The TRIDENT Study). Circ. Res. 121, 1279-1290.   DOI
5 Gralla, J., Brekenfeld, C., Mordasini, P. and Schroth, G. 2012. Mechanical thrombolysis and stenting in acute ischemic stroke. Stroke 43, 280-285.   DOI
6 Gupta, P. K., Chullikana, A., Parakh, R., Desai, S., Das, A. and Majumdar, A. S. 2013. A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia. J. Transl. Med. 11, 143.   DOI
7 Gupta, P. K., Krishna, M., Chullikana, A., Desai, S., Murugesan, R. and Majumdar, A. S. 2017. Administration of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells in critical limb Ischemia due to Buerger's disease: Phase II study report suggests clinical efficacy. Stem Cells Transl Med. 6, 689-699.   DOI
8 Haack-Sorensen, M., Friis, T., Mathiasen, A. B., Jorgensen, E., Hansen, L. and Kastrup, J. 2013. Direct intramyocardial mesenchymal stromal cell injections in patients with severe refractory angina: one-year follow-up. Cell Transplant. 22, 521-528.   DOI
9 Heo, S. C., Kwon, Y. W., Park, G. T., Kwon, S. M., Bae, S. S. and Kim, J. H. 2020. Mesenchymal stem cell-mediated therapy of peripheral artery disease is stimulated by a lamin A-Progerin binding inhibitor. J. Lipid Atheroscler. 9, 460-473.   DOI
10 Hess, D. C., Wechsler, L. R., Clark, W. M., Savitz, S. I., Ford, G. A. and Mays, R. W. 2017. Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 16, 360-368.   DOI
11 Honmou, O., Houkin, K., Matsunaga, T., Niitsu, Y., Ishiai, S. and Kocsis, J. D. 2011. Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke. Brain 134, 1790-1807.   DOI
12 Huang, Z., Nooeaid, P., Kohl, B., Roether, J. A., Schubert, D. W. and Schulze-Tanzil, G. 2015. Chondrogenesis of human bone marrow mesenchymal stromal cells in highly porous alginate-foams supplemented with chondroitin sulfate. Mater. Sci. Eng. C Mater. Biol. Appl. 50, 160-172.   DOI
13 Ikhapoh, I. A., Pelham, C. J. and Agrawal, D. K. 2015. Srytype HMG box 18 contributes to the differentiation of bone marrow-derived mesenchymal stem cells to endothelial cells. Differentiation 89, 87-96.   DOI
14 Jeong, H., Yim, H. W., Park, H. J., Cho, Y., Hong, H. and Oh, I. H. 2018. Mesenchymal stem cell therapy for Ischemic Heart Disease: Systematic review and metaanalysis. Int. J. Stem Cells 11, 1-12.   DOI
15 Bae, K. S., Park, J. B., Kim, H. S., Kim, D. S., Park, D. J. and Kang, S. J. 2011. Neuron-like differentiation of bone marrow-derived mesenchymal stem cells. Yonsei Med. J. 52, 401-412.   DOI
16 Najar, M., Raicevic, G., Fayyad-Kazan, H., Bron, D., Toungouz, M. and Lagneaux, L. 2016. Mesenchymal stromal cells and immunomodulation: A gathering of regulatory immune cells. Cytotherapy 18, 160-171.   DOI
17 Pievani, A., Scagliotti, V., Russo, F. M., Azario, I., Rambaldi, B. and Serafini, M. 2014. Comparative analysis of multilineage properties of mesenchymal stromal cells derived from fetal sources shows an advantage of mesenchymal stromal cells isolated from cord blood in chondrogenic differentiation potential. Cytotherapy 16, 893-905.   DOI
18 Ra, J. C., Shin, I. S., Kim, S. H., Kang, S. K., Kang, B. C. and Kwon, E. 2011. Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem Cells Dev. 20, 1297-1308.   DOI
19 Bago, J. R., Alieva, M., Soler, C., Rubio, N. and Blanco, J. 2013. Endothelial differentiation of adipose tissue-derived mesenchymal stromal cells in glioma tumors: implications for cell-based therapy. Mol. Ther. 21, 1758-1766.   DOI
20 El-Ansary, M., Abdel-Aziz, I., Mogawer, S., Abdel-Hamid, S., Hammam, O. and Wahdan, M. 2012. Phase II trial: undifferentiated versus differentiated autologous mesenchymal stem cells transplantation in Egyptian patients with HCV induced liver cirrhosis. Stem Cell Rev. Rep. 8, 972-981.   DOI
21 Bartunek, J., Terzic, A., Davison, B. A., Filippatos, G. S., Radovanovic, S. and Program, C. 2017. Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, shamcontrolled CHART-1 clinical trial. Eur. Heart J. 38, 648-660.   DOI
22 Choudhery, M. S., Badowski, M., Muise, A. and Harris, D. T. 2013. Comparison of human mesenchymal stem cells derived from adipose and cord tissue. Cytotherapy 15, 330-343.   DOI
23 Chullikana, A., Majumdar, A. S., Gottipamula, S., Krishnamurthy, S., Kumar, A. S. and Gupta, P. K. 2015. Randomized, double-blind, phase I/II study of intravenous allogeneic mesenchymal stromal cells in acute myocardial infarction. Cytotherapy 17, 250-261.   DOI
24 Qayyum, A. A., Mathiasen, A. B., Helqvist, S., Jorgensen, E., Haack-Sorensen, M. and Kastrup, J. 2019. Autologous adipose-derived stromal cell treatment for patients with refractory angina (MyStromalCell Trial): 3-years follow-up results. J. Transl. Med. 17, 360.   DOI
25 Bartolucci, J., Verdugo, F. J., Gonzalez, P. L., Larrea, R. E., Abarzua, E. and Khoury, M. 2017. Safety and efficacy of the intravenous infusion of umbilical cord mesenchymal stem cells in patients with heart failure: a phase 1/2 randomized controlled trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]). Circ. Res. 121, 1192-1204.   DOI
26 Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R. and Marshak, D. R. 1999. Multilineage potential of adult human mesenchymal stem cells. Science 284, 143-147.   DOI
27 Premer, C., Blum, A., Bellio, M. A., Schulman, I. H., Hurwitz, B. E. and Hare, J. M. 2015. Allogeneic Mesenchymal stem cells restore endothelial function in heart failure by stimulating endothelial progenitor cells. EBioMedicine 2, 467-475.   DOI
28 Qayyum, A. A., Mathiasen, A. B., Mygind, N. D., Kuhl, J. T., Jorgensen, E. and Kastrup, J. 2017. Adipose-derived stromal cells for treatment of patients with chronic Ischemic Heart Disease (MyStromalCell Trial): a randomized Placebo-controlled study. Stem Cells Int. 2017, 5237063.   DOI
29 Li, W., Shi, L., Hu, B., Hong, Y., Zhang, H. and Zhang, Y. 2021. Mesenchymal stem cell-based therapy for stroke: current understanding and challenges. Front. Cell. Neurosci. 15, 628940.   DOI
30 Lalu, M. M., McIntyre, L., Pugliese, C., Fergusson, D., Winston, B. W. and Canadian Critical Care Trials, G. 2012. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One 7, e47559.   DOI
31 Chang, D., Fan, T., Gao, S., Jin, Y., Zhang, M. and Ono, M. 2021. Application of mesenchymal stem cell sheet to treatment of ischemic heart disease. Stem Cell. Res. Ther. 12, 384.   DOI
32 Rashed, L. A., Elattar, S., Eltablawy, N., Ashour, H., Mahmoud, L. M. and El-Esawy, Y. 2018. Mesenchymal stem cells pretreated with melatonin ameliorate kidney functions in a rat model of diabetic nephropathy. Biochem. Cell Biol. 96, 564-571.   DOI
33 Ascheim, D. D., Gelijns, A. C., Goldstein, D., Moye, L. A., Smedira, N. and Woo, Y. J. 2014. Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices. Circulation 129, 2287-2296.   DOI
34 Bang, O. Y., Lee, J. S., Lee, P. H. and Lee, G. 2005. Autologous mesenchymal stem cell transplantation in stroke patients. Ann. Neurol. 57, 874-882.   DOI
35 Chung, C. S., Fujita, N., Kawahara, N., Yui, S., Nam, E. and Nishimura, R. 2013. A comparison of neurosphere differentiation potential of canine bone marrow-derived mesenchymal stem cells and adipose-derived mesenchymal stem cells. J. Vet. Med. Sci. 75, 879-886.   DOI
36 Heldman, A. W., DiFede, D. L., Fishman, J. E., Zambrano, J. P., Trachtenberg, B. H. and Hare, J. M. 2014. Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial. JAMA. 311, 62-73.   DOI
37 Kim, J. Y., Lee, J. S., Han, Y. S., Lee, J. H., Bae, I. and Lee, S. H. 2015. Pretreatment with lycopene attenuates oxidative stress-induced apoptosis in human mesenchymal stem cells. Biomol. Ther. (Seoul). 23, 517-524.   DOI
38 Friedenstein, A. J., Deriglasova, U. F., Kulagina, N. N., Panasuk, A. F., Rudakowa, S. F. and Ruadkow, I. A. 1974. Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method. Exp. Hematol. 2, 83-92.
39 Jiang, C. Y., Gui, C., He, A. N., Hu, X. Y., Chen, J. and Wang, J. A. 2008. Optimal time for mesenchymal stem cell transplantation in rats with myocardial infarction. J. Zhejiang Univ. Sci. B. 9, 630-637.   DOI
40 Kabat, M., Bobkov, I., Kumar, S. and Grumet, M. 2020. Trends in mesenchymal stem cell clinical trials 2004-2018: Is efficacy optimal in a narrow dose range? Stem Cells Transl. Med. 9, 17-27.   DOI
41 Kouroupis, D., Willman, M. A., Best, T. M., Kaplan, L. D. and Correa, D. 2021. Infrapatellar fat pad-derived mesenchymal stem cell-based spheroids enhance their therapeutic efficacy to reverse synovitis and fat pad fibrosis. Stem Cell. Res. Ther. 12, 44.   DOI
42 Hou, L., Cao, H., Wang, D., Wei, G., Bai, C. and Pei, X. 2003. Induction of umbilical cord blood mesenchymal stem cells into neuron-like cells in vitro. Int. J. Hematol. 78, 256-261.   DOI
43 De Becker, A. and Riet, I. V. 2016. Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy? World J. Stem Cells 8, 73-87.
44 Eseonu, O. I. and De Bari, C. 2015. Homing of mesenchymal stem cells: mechanistic or stochastic? Implications for targeted delivery in arthritis. Rheumatology (Oxford) 54, 210-218.   DOI
45 Gao, W. H., Gao, H. Y., Li, Y. T. and Huang, P. P. 2019. Effectiveness of umbilical cord mesenchymal stem cells in patients with critical limb ischemia. Med. Clin. (Barc.). 153, 341-346.   DOI
46 Jaillard, A., Hommel, M., Moisan, A., Zeffiro, T. A., FavreWiki, I. M. and Detante, O. 2020. Autologous mesenchymal stem cells improve motor recovery in subacute Ischemic stroke: a randomized clinical trial. Transl Stroke Res. 11, 910-923.   DOI
47 Wakitani, S., Saito, T. and Caplan, A. I. 1995. Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve 18, 1417-1426.   DOI
48 Tebebi, P. A., Kim, S. J., Williams, R. A., Milo, B., Frenkel, V. and Frank, J. A. 2017. Improving the therapeutic efficacy of mesenchymal stromal cells to restore perfusion in critical limb ischemia through pulsed focused ultrasound. Sci. Rep. 7, 41550.   DOI
49 Ullah, M., Liu, D. D. and Thakor, A. S. 2019. Mesenchymal stromal cell homing: mechanisms and strategies for improvement. iScience 15, 421-438.   DOI
50 Urrutia, D. N., Caviedes, P., Mardones, R., Minguell, J. J., Vega-Letter, A. M. and Jofre, C. M. 2019. Comparative study of the neural differentiation capacity of mesenchymal stromal cells from different tissue sources: An approach for their use in neural regeneration therapies. PLoS One 14, e0213032.   DOI
51 Wang, J., Zeng, X. X., Cai, W., Han, Z. B., Zhu, L. Y. and Xu, J. X. 2021. Safety and efficacy of placenta-derived mesenchymal stem cell treatment for diabetic patients with critical limb Ischemia: a pilot study. Exp. Clin. Endocrinol. Diabetes 129, 542-548.   DOI
52 Liew, A. and O'Brien, T. 2012. Therapeutic potential for mesenchymal stem cell transplantation in critical limb ischemia. Stem Cell. Res. Ther. 3, 28.   DOI
53 Lee, J. S., Hong, J. M., Moon, G. J., Lee, P. H., Ahn, Y. H. and Collaborators, S. 2010. A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells 28, 1099-1106.   DOI
54 Wu, Y. N., Law, J. B., He, A. Y., Low, H. Y., Hui, J. H. and Lee, E. H. 2014. Substrate topography determines the fate of chondrogenesis from human mesenchymal stem cells resulting in specific cartilage phenotype formation. Nanomedicine 10, 1507-1516.   DOI
55 Xu, W., Zhang, X., Qian, H., Zhu, W., Sun, X. and Chen, Y. 2004. Mesenchymal stem cells from adult human bone marrow differentiate into a cardiomyocyte phenotype in vitro. Exp. Biol. Med. (Maywood) 229, 623-631.   DOI
56 Yang, J., Song, T., Wu, P., Chen, Y., Fan, X. and Huang, C. 2012. Differentiation potential of human mesenchymal stem cells derived from adipose tissue and bone marrow to sinus node-like cells. Mol. Med. Rep. 5, 108-113.   DOI
57 Lee, S. C., Jeong, H. J., Lee, S. K. and Kim, S. J. 2015. Lipopolysaccharide preconditioning of adipose-derived stem cells improves liver-regenerating activity of the secretome. Stem Cell. Res. Ther. 6, 75.   DOI
58 Lei, H., Yu, B., Huang, Z., Yang, X., Liu, Z. and Chen, D. 2013. Comparative analysis of mesenchymal stem cells from adult mouse adipose, muscle, and fetal muscle. Mol. Biol. Rep. 40, 885-892.   DOI
59 Li, S., Wang, X., Li, J., Zhang, J., Zhang, F. and Li, Q. 2016. Advances in the treatment of Ischemic Diseases by mesenchymal stem cells. Stem Cells Int. 2016, 5896061.
60 Sangiorgi, B., De Freitas, H. T., Schiavinato, J. L., Leao, V., Haddad, R. and Panepucci, R. A. 2016. DSP30 enhances the immunosuppressive properties of mesenchymal stromal cells and protects their suppressive potential from lipopolysaccharide effects: A potential role of adenosine. Cytotherapy 18, 846-859.   DOI
61 Saqqur, M., Uchino, K., Demchuk, A. M., Molina, C. A., Garami, Z. and Investigators, C. 2007. Site of arterial occlusion identified by transcranial Doppler predicts the response to intravenous thrombolysis for stroke. Stroke 38, 948-954.   DOI
62 Herrmann, R., Sturm, M., Shaw, K., Purtill, D., Cooney, J. and Cannell, P. 2012. Mesenchymal stromal cell therapy for steroid-refractory acute and chronic graft versus host disease: a phase 1 study. Int. J. Hematol. 95, 182-188.   DOI
63 Sibov, T. T., Severino, P., Marti, L. C., Pavon, L. F., Oliveira, D. M. and Moreira-Filho, C. A. 2012. Mesenchymal stem cells from umbilical cord blood: parameters for isolation, characterization and adipogenic differentiation. Cytotechnology 64, 511-521.   DOI
64 Steinberg, G. K., Kondziolka, D., Wechsler, L. R., Lunsford, L. D., Kim, A. S. and Schwartz, N. E. 2018. Two-year safety and clinical outcomes in chronic ischemic stroke patients after implantation of modified bone marrow-derived mesenchymal stem cells (SB623): a phase 1/2a study. J. Neurosurg. 131, 1462-1472.   DOI
65 Guijarro, D., Lebrin, M., Lairez, O., Bourin, P., Piriou, N. and Roncalli, J. 2016. Intramyocardial transplantation of mesenchymal stromal cells for chronic myocardial ischemia and impaired left ventricular function: Results of the MESAMI 1 pilot trial. Int. J. Cardiol. 209, 258-265.   DOI
66 Gutierrez-Fernandez, M., Rodriguez-Frutos, B., Otero-Ortega, L., Ramos-Cejudo, J., Fuentes, B. and Diez-Tejedor, E. 2013. Adipose tissue-derived stem cells in stroke treatment: from bench to bedside. Discov. Med. 16, 37-43.
67 Hare, J. M., Fishman, J. E., Gerstenblith, G., DiFede Velazquez, D. L., Zambrano, J. P. and Lardo, A. 2012. Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA. 308, 2369-2379.   DOI
68 Ikhapoh, I. A., Pelham, C. J. and Agrawal, D. K. 2015. Synergistic effect of angiotensin II on vascular endothelial growth factor-A-mediated differentiation of bone marrow-derived mesenchymal stem cells into endothelial cells. Stem Cell. Res. Ther. 6, 4.   DOI
69 Ji, S. T., Kim, H., Yun, J., Chung, J. S. and Kwon, S. M. 2017. Promising therapeutic strategies for mesenchymal stem cell-based cardiovascular regeneration: from cell priming to tissue engineering. Stem Cells Int. 2017, 3945403.   DOI
70 Khazaei, M., Davoodian, A., Taheri, M. and Ghafouri-Fard, S. 2020. Former antiplatelet drug administration and consequences of intravenous thrombolysis in acute ischemic stroke. Hum. Antibodies 28, 53-56.   DOI
71 Kyurkchiev, D., Bochev, I., Ivanova-Todorova, E., Mourdjeva, M., Oreshkova, T. and Kyurkchiev, S. 2014. Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J. Stem Cells 6, 552-570.   DOI
72 Su, Y. H., Chen, C. H., Lin, H. J., Chen, Y. W., Tseng, M. C. and Sung, S. F. 2017. Safety and effectiveness of intravenous thrombolysis for acute Ischemic stroke outside the coverage of national health insurance in Taiwan. Acta Neurol. Taiwan 26, 3-12.
73 Yin, F., Wang, W. Y. and Jiang, W. H. 2019. Human umbilical cord mesenchymal stem cells ameliorate liver fibrosis in vitro and in vivo: From biological characteristics to therapeutic mechanisms. World J. Stem Cells 11, 548-564.   DOI
74 Yu, H., Lu, K., Zhu, J. and Wang, J. 2017. Stem cell therapy for ischemic heart diseases. Br. Med. Bull. 121, 135-154.   DOI
75 Yu, J., Du, K. T., Fang, Q., Gu, Y., Mihardja, S. S. and Lee, R. J. 2010. The use of human mesenchymal stem cells encapsulated in RGD modified alginate microspheres in the repair of myocardial infarction in the rat. Biomaterials 31, 7012-7020.   DOI
76 Zhao, D., Cui, D., Wang, B., Tian, F., Guo, L. and Yu, X. 2012. Treatment of early stage osteonecrosis of the femoral head with autologous implantation of bone marrow-derived and cultured mesenchymal stem cells. Bone 50, 325-330.   DOI
77 Zhu, H., Guo, Z. K., Jiang, X. X., Li, H., Wang, X. Y. and Mao, N. 2010. A protocol for isolation and culture of mesenchymal stem cells from mouse compact bone. Nat. Protoc. 5, 550-560.   DOI
78 Mackenzie, T. C. and Flake, A. W. 2001. Multilineage differentiation of human MSC after in utero transplantation. Cytotherapy 3, 403-405.   DOI
79 Liu, C. B., Huang, H., Sun, P., Ma, S. Z., Liu, A. H. and Zhang, X. Z. 2016. Human umbilical cord-derived mesenchymal stromal cells improve left ventricular function, perfusion, and remodeling in a porcine model of chronic myocardial Ischemia. Stem Cells Transl. Med. 5, 1004-1013.   DOI
80 Lu, D., Jiang, Y., Deng, W., Zhang, Y., Liang, Z. and Xue, Y. 2019. Long-term outcomes of BMMSC compared with BMMNC for treatment of critical limb Ischemia and foot ulcer in patients with diabetes. Cell Transplant. 28, 645-652.   DOI
81 Mao, P., Joshi, K., Li, J., Kim, S. H., Li, P. and Nakano, I. 2013. Mesenchymal glioma stem cells are maintained by activated glycolytic metabolism involving aldehyde dehydrogenase 1A3. Proc. Natl. Acad. Sci. USA. 110, 8644-8649.   DOI
82 Schmehl, J., Stoll, H., Danalache, M., Grozinger, G. C., Greiner, T. O. and Elser, S. 2021. Intravascular application of labelled cell spheroids: an approach for Ischemic peripheral artery disease. Int. J. Mol. Sci. 22, 6831.   DOI
83 Zuk, P. A., Zhu, M., Ashjian, P., De Ugarte, D. A., Huang, J. I. and Hedrick, M. H. 2002. Human adipose tissue is a source of multipotent stem cells. Mol. Biol. Cell 13, 4279-4295.   DOI
84 Zhang, K., Zhao, X., Chen, X., Wei, Y., Du, W. and Li, Z. 2018. Enhanced therapeutic effects of Mesenchymal stem cell-derived exosomes with an injectable hydrogel for Hindlimb Ischemia treatment. ACS Appl. Mater. Interfaces 10, 30081-30091.   DOI
85 Seifert, A., Werheid, D. F., Knapp, S. M. and Tobiasch, E. 2015. Role of Hox genes in stem cell differentiation. World J. Stem Cells 7, 583-595.   DOI
86 Williams, A. R., Trachtenberg, B., Velazquez, D. L., Mc Niece, I., Altman, P. and Hare, J. M. 2011. Intramyocardial stem cell injection in patients with ischemic cardiomyopathy: functional recovery and reverse remodeling. Circ. Res. 108, 792-796.   DOI
87 Shuai, Y., Liao, L., Su, X., Yu, Y., Shao, B. and Jin, Y. 2016. Melatonin treatment improves mesenchymal stem cells therapy by preserving stemness during long-term in vitro expansion. Theranostics 6, 1899-1917.   DOI
88 Silva, G. V., Litovsky, S., Assad, J. A., Sousa, A. L., Martin, B. J. and Perin, E. C. 2005. Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 111, 150-156.   DOI
89 Smadja, D. M., d'Audigier, C., Guerin, C. L., Mauge, L., Dizier, B. and Emmerich, J. 2012. Angiogenic potential of BM MSCs derived from patients with critical leg ischemia. Bone Marrow Transplant. 47, 997-1000.   DOI
90 Mathiasen, A. B., Qayyum, A. A., Jorgensen, E., Helqvist, S., Fischer-Nielsen, A. and Kastrup, J. 2015. Bone marrow-derived mesenchymal stromal cell treatment in patients with severe ischaemic heart failure: a randomized placebo-controlled trial (MSC-HF trial). Eur. Heart J. 36, 1744-1753.   DOI
91 Noronha, N. C., Mizukami, A., Caliari-Oliveira, C., Cominal, J. G., Rocha, J. L. M. and Malmegrim, K. C. R. 2019. Priming approaches to improve the efficacy of mesenchymal stromal cell-based therapies. Stem Cell. Res. Ther. 10, 131.   DOI
92 Park, B. W., Jung, S. H., Das, S., Lee, S. M., Park, J. H. and Park, H. J. 2020. In vivo priming of human mesenchymal stem cells with hepatocyte growth factor-engineered mesenchymal stem cells promotes therapeutic potential for cardiac repair. Sci. Adv. 6, eaay6994.   DOI
93 Perin, E. C., Sanz-Ruiz, R., Sanchez, P. L., Lasso, J., Perez-Cano, R. and Fernandez-Aviles, F. 2014. Adipose-derived regenerative cells in patients with ischemic cardiomyopathy: The PRECISE Trial. Am. Heart J. 168, 88-95. e82.   DOI
94 Gutierrez-Fernandez, M., Rodriguez-Frutos, B., RamosCejudo, J., Teresa Vallejo-Cremades, M., Fuentes, B. and Diez-Tejedor, E. 2013. Effects of intravenous administration of allogenic bone marrowand adipose tissue-derived mesenchymal stem cells on functional recovery and brain repair markers in experimental ischemic stroke. Stem Cell. Res. Ther. 4, 11.   DOI