Stem Cell–Based Therapies: What Interventional Radiologists Need to Know

Hyeon Yu; Clayton W. Commander; Joseph M. Stavas

doi:10.1055/s-0041-1736657

Seminars in Interventional Radiology, Table of Contents

Semin intervent Radiol 2021; 38(05): 523-534
DOI: 10.1055/s-0041-1736657

Review Article

Stem Cell–Based Therapies: What Interventional Radiologists Need to Know

Hyeon Yu

¹Division of Vascular and Interventional Radiology, Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina

,

Clayton W. Commander

¹Division of Vascular and Interventional Radiology, Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina

,

Joseph M. Stavas

²Department of Radiology, Creighton University School of Medicine, Omaha, Nebraska

³ProKidney LLC, Winston Salem, North Carolina

› Author Affiliations

Abstract

As the basic units of biological organization, stem cells and their progenitors are essential for developing and regenerating organs and tissue systems using their unique self-renewal capability and differentiation potential into multiple cell lineages. Stem cells are consistently present throughout the entire human development, from the zygote to adulthood. Over the past decades, significant efforts have been made in biology, genetics, and biotechnology to develop stem cell–based therapies using embryonic and adult autologous or allogeneic stem cells for diseases without therapies or difficult to treat. Stem cell–based therapies require optimum administration of stem cells into damaged organs to promote structural regeneration and improve function. Maximum clinical efficacy is highly dependent on the successful delivery of stem cells to the target tissue. Direct image-guided locoregional injections into target tissues offer an option to increase therapeutic outcomes. Interventional radiologists have the opportunity to perform a key role in delivering stem cells more efficiently using minimally invasive techniques. This review discusses the types and sources of stem cells and the current clinical applications of stem cell–based therapies. In addition, the regulatory considerations, logistics, and potential roles of interventional Radiology are also discussed with the review of the literature.

Keywords

stem cells - progenitor cells - stem cell–based therapy - interventional radiology

Full Text

References

References
1 Becker AJ, McCulloch EA, Till JE. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 1963; 197: 452-454
2 McCulloch EA, Till JE. The radiation sensitivity of normal mouse bone marrow cells, determined by quantitative marrow transplantation into irradiated mice. Radiat Res 1960; 13: 115-125
3 Ratajczak MZ, Bujko K, Wojakowski W. Stem cells and clinical practice: new advances and challenges at the time of emerging problems with induced pluripotent stem cell therapies. Pol Arch Med Wewn 2016; 126 (11) 879-890
4 Mitalipov S, Wolf D. Totipotency, pluripotency and nuclear reprogramming. Adv Biochem Eng Biotechnol 2009; 114: 185-199
5 Condic ML. Totipotency: what it is and what it is not. Stem Cells Dev 2014; 23 (08) 796-812
6 Ratajczak MZ, Zuba-Surma E, Kucia M, Poniewierska A, Suszynska M, Ratajczak J. Pluripotent and multipotent stem cells in adult tissues. Adv Med Sci 2012; 57 (01) 1-17
7 Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature 1981; 292 (5819): 154-156
8 Mendonça LS, Onofre I, Miranda CO, Perfeito R, Nóbrega C, de Almeida LP. Stem cell-based therapies for polyglutamine diseases. Adv Exp Med Biol 2018; 1049: 439-466
9 Thomson JA, Itskovitz-Eldor J, Shapiro SS. et al. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282 (5391): 1145-1147
10 Cui H, Tang D, Garside GB. et al. Wnt signaling mediates the aging-induced differentiation impairment of intestinal stem cells. Stem Cell Rev Rep 2019; 15 (03) 448-455
11 Soleimani M, Nadri S. A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow. Nat Protoc 2009; 4 (01) 102-106
12 Schneider S, Unger M, van Griensven M, Balmayor ER. Adipose-derived mesenchymal stem cells from liposuction and resected fat are feasible sources for regenerative medicine. Eur J Med Res 2017; 22 (01) 17
13 Di Scipio F, Sprio AE, Carere ME, Yang Z, Berta GN. A simple protocol to isolate, characterize, and expand dental pulp stem cells. Methods Mol Biol 2017; 1553: 1-13
14 Ueno Y, Koizumi S, Yamagami M, Miura M, Taniguchi N. Characterization of hemopoietic stem cells (CFUc) in cord blood. Exp Hematol 1981; 9 (07) 716-722
15 Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126 (04) 663-676
16 Shi Y, Inoue H, Wu JC, Yamanaka S. Induced pluripotent stem cell technology: a decade of progress. Nat Rev Drug Discov 2017; 16 (02) 115-130
17 Kimbrel EA, Lanza R. Next-generation stem cells - ushering in a new era of cell-based therapies. Nat Rev Drug Discov 2020; 19 (07) 463-479
18 Rubin LL, Haston KM. Stem cell biology and drug discovery. BMC Biol 2011; 9: 42
19 Wang Y, Yin P, Bian GL. et al. The combination of stem cells and tissue engineering: an advanced strategy for blood vessels regeneration and vascular disease treatment. Stem Cell Res Ther 2017; 8 (01) 194
20 Pera MF, Reubinoff B, Trounson A. Human embryonic stem cells. J Cell Sci 2000; 113 (Pt 1): 5-10
21 Niakan KK, Han J, Pedersen RA, Simon C, Pera RA. Human pre-implantation embryo development. Development 2012; 139 (05) 829-841
22 Eiselleova L, Peterkova I, Neradil J, Slaninova I, Hampl A, Dvorak P. Comparative study of mouse and human feeder cells for human embryonic stem cells. Int J Dev Biol 2008; 52 (04) 353-363
23 Klimanskaya I, Chung Y, Meisner L, Johnson J, West MD, Lanza R. Human embryonic stem cells derived without feeder cells. Lancet 2005; 365 (9471): 1636-1641
24 Suemori H, Yasuchika K, Hasegawa K, Fujioka T, Tsuneyoshi N, Nakatsuji N. Efficient establishment of human embryonic stem cell lines and long-term maintenance with stable karyotype by enzymatic bulk passage. Biochem Biophys Res Commun 2006; 345 (03) 926-932
25 Priester C, MacDonald A, Dhar M, Bow A. Examining the characteristics and applications of mesenchymal, induced pluripotent, and embryonic stem cells for tissue engineering approaches across the germ layers. Pharmaceuticals (Basel) 2020; 13 (11) E344
26 Isasi RM. Policy interoperability in stem cell research: demystifying harmonization. Stem Cell Rev Rep 2009; 5 (02) 108-115
27 Xie X, Chen J, Shu Z. From strict moral standards to ethical neutrality: a policy-guided shift in the patentability of human embryonic stem cells in China. Stem Cell Res Ther 2020; 11 (01) 499
28 Carpenter MK, Rao MS. Concise review: making and using clinically compliant pluripotent stem cell lines. Stem Cells Transl Med 2015; 4 (04) 381-388
29 English K, Wood KJ. Immunogenicity of embryonic stem cell-derived progenitors after transplantation. Curr Opin Organ Transplant 2011; 16 (01) 90-95
30 Thompson HL, Manilay JO. Embryonic stem cell-derived hematopoietic stem cells: challenges in development, differentiation, and immunogenicity. Curr Top Med Chem 2011; 11 (13) 1621-1637
31 Storchová Z. Too much to differentiate: aneuploidy promotes proliferation and teratoma formation in embryonic stem cells. EMBO J 2016; 35 (21) 2265-2267
32 Stachelscheid H, Wulf-Goldenberg A, Eckert K. et al. Teratoma formation of human embryonic stem cells in three-dimensional perfusion culture bioreactors. J Tissue Eng Regen Med 2013; 7 (09) 729-741
33 Pittenger MF, Mackay AM, Beck SC. et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284 (5411): 143-147
34 Poulsom R, Alison MR, Forbes SJ, Wright NA. Adult stem cell plasticity. J Pathol 2002; 197 (04) 441-456
35 Graf T, Stadtfeld M. Heterogeneity of embryonic and adult stem cells. Cell Stem Cell 2008; 3 (05) 480-483
36 Arai F, Hirao A, Ohmura M. et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 2004; 118 (02) 149-161
37 Morrison SJ, Kimble J. Asymmetric and symmetric stem-cell divisions in development and cancer. Nature 2006; 441 (7097): 1068-1074
38 Visvader JE, Clevers H. Tissue-specific designs of stem cell hierarchies. Nat Cell Biol 2016; 18 (04) 349-355
39 Kuçi S, Kuçi Z, Latifi-Pupovci H. et al. Adult stem cells as an alternative source of multipotential (pluripotential) cells in regenerative medicine. Curr Stem Cell Res Ther 2009; 4 (02) 107-117
40 Bryder D, Rossi DJ, Weissman IL. Hematopoietic stem cells: the paradigmatic tissue-specific stem cell. Am J Pathol 2006; 169 (02) 338-346
41 Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature 2014; 505 (7483): 327-334
42 Rodríguez-Fuentes DE, Fernández-Garza LE, Samia-Meza JA, Barrera-Barrera SA, Caplan AI, Barrera-Saldaña HA. Mesenchymal stem cells current clinical applications: a systematic review. Arch Med Res 2021; 52 (01) 93-101
43 Nombela-Arrieta C, Ritz J, Silberstein LE. The elusive nature and function of mesenchymal stem cells. Nat Rev Mol Cell Biol 2011; 12 (02) 126-131
44 Chen WC, Baily JE, Corselli M. et al. Human myocardial pericytes: multipotent mesodermal precursors exhibiting cardiac specificity. Stem Cells 2015; 33 (02) 557-573
45 Stefanska A, Kenyon C, Christian HC. et al. Human kidney pericytes produce renin. Kidney Int 2016; 90 (06) 1251-1261
46 Shi S, Gronthos S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone Miner Res 2003; 18 (04) 696-704
47 Fitzsimmons REB, Mazurek MS, Soos A, Simmons CA. Mesenchymal stromal/stem cells in regenerative medicine and tissue engineering. Stem Cells Int 2018; 2018: 8031718
48 Mushtaq M, DiFede DL, Golpanian S. et al. Rationale and design of the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy (the POSEIDON-DCM study): a phase I/II, randomized pilot study of the comparative safety and efficacy of transendocardial injection of autologous mesenchymal stem cell vs. allogeneic mesenchymal stem cells in patients with non-ischemic dilated cardiomyopathy. J Cardiovasc Transl Res 2014; 7 (09) 769-780
49 Lalu MM, McIntyre L, Pugliese C. et al; Canadian Critical Care Trials Group. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One 2012; 7 (10) e47559
50 Dominici M, Le Blanc K, Mueller I. et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8 (04) 315-317
51 Ciuffreda MC, Malpasso G, Musarò P, Turco V, Gnecchi M. Protocols for in vitro differentiation of human mesenchymal stem cells into osteogenic, chondrogenic and adipogenic lineages. Methods Mol Biol 2016; 1416: 149-158
52 Vater C, Kasten P, Stiehler M. Culture media for the differentiation of mesenchymal stromal cells. Acta Biomater 2011; 7 (02) 463-477
53 Guimarães-Camboa N, Cattaneo P, Sun Y. et al. Pericytes of multiple organs do not behave as mesenchymal stem cells in vivo. Cell Stem Cell 2017; 20 (03) 345-359.e5
54 Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell 2011; 9 (01) 11-15
55 Nassiri SM, Rahbarghazi R. Interactions of mesenchymal stem cells with endothelial cells. Stem Cells Dev 2014; 23 (04) 319-332
56 Tao H, Han Z, Han ZC, Li Z. Proangiogenic features of mesenchymal stem cells and their therapeutic applications. Stem Cells Int 2016; 2016: 1314709
57 Phinney DG, Pittenger MF. Concise review: MSC-derived exosomes for cell-free therapy. Stem Cells 2017; 35 (04) 851-858
58 Zhao X, Moore DL. Neural stem cells: developmental mechanisms and disease modeling. Cell Tissue Res 2018; 371 (01) 1-6
59 Bond AM, Ming GL, Song H. Adult mammalian neural stem cells and neurogenesis: five decades later. Cell Stem Cell 2015; 17 (04) 385-395
60 Galvan V, Jin K. Neurogenesis in the aging brain. Clin Interv Aging 2007; 2 (04) 605-610
61 Doetsch F, Caillé I, Lim DA, García-Verdugo JM, Alvarez-Buylla A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 1999; 97 (06) 703-716
62 Takagi Y. History of neural stem cell research and its clinical application. Neurol Med Chir (Tokyo) 2016; 56 (03) 110-124
63 Sun GJ, Zhou Y, Stadel RP. et al. Tangential migration of neuronal precursors of glutamatergic neurons in the adult mammalian brain. Proc Natl Acad Sci U S A 2015; 112 (30) 9484-9489
64 Nakayama D, Matsuyama T, Ishibashi-Ueda H. et al. Injury-induced neural stem/progenitor cells in post-stroke human cerebral cortex. Eur J Neurosci 2010; 31 (01) 90-98
65 Chen J, Shehadah A, Pal A. et al. Neuroprotective effect of human placenta-derived cell treatment of stroke in rats. Cell Transplant 2013; 22 (05) 871-879
66 Chen QQ, Yan L, Wang CZ. et al. Mesenchymal stem cells alleviate TNBS-induced colitis by modulating inflammatory and autoimmune responses. World J Gastroenterol 2013; 19 (29) 4702-4717
67 Medina RJ, Barber CL, Sabatier F. et al. Endothelial progenitors: a consensus statement on nomenclature. Stem Cells Transl Med 2017; 6 (05) 1316-1320
68 Goligorsky MS, Salven P. Concise review: endothelial stem and progenitor cells and their habitats. Stem Cells Transl Med 2013; 2 (07) 499-504
69 Slukvin II, Kumar A. The mesenchymoangioblast, mesodermal precursor for mesenchymal and endothelial cells. Cell Mol Life Sci 2018; 75 (19) 3507-3520
70 Zovein AC, Hofmann JJ, Lynch M. et al. Fate tracing reveals the endothelial origin of hematopoietic stem cells. Cell Stem Cell 2008; 3 (06) 625-636
71 Adams RH, Alitalo K. Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol 2007; 8 (06) 464-478
72 Chong MS, Ng WK, Chan JK. Concise review: endothelial progenitor cells in regenerative medicine: applications and challenges. Stem Cells Transl Med 2016; 5 (04) 530-538
73 Asahara T, Murohara T, Sullivan A. et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275 (5302): 964-967
74 Sun K, Zhou Z, Ju X. et al. Combined transplantation of mesenchymal stem cells and endothelial progenitor cells for tissue engineering: a systematic review and meta-analysis. Stem Cell Res Ther 2016; 7 (01) 151
75 Ahmed TA, El-Badri N. Pericytes: the role of multipotent stem cells in vascular maintenance and regenerative medicine. Adv Exp Med Biol 2018; 1079: 69-86
76 Sims DE. The pericyte–a review. Tissue Cell 1986; 18 (02) 153-174
77 Díaz-Flores L, Gutiérrez R, Madrid JF. et al. Pericytes. Morphofunction, interactions and pathology in a quiescent and activated mesenchymal cell niche. Histol Histopathol 2009; 24 (07) 909-969
78 Armulik A, Genové G, Betsholtz C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 2011; 21 (02) 193-215
79 Bergwerff M, Verberne ME, DeRuiter MC, Poelmann RE, Gittenberger-de Groot AC. Neural crest cell contribution to the developing circulatory system: implications for vascular morphology?. Circ Res 1998; 82 (02) 221-231
80 Creazzo TL, Godt RE, Leatherbury L, Conway SJ, Kirby ML. Role of cardiac neural crest cells in cardiovascular development. Annu Rev Physiol 1998; 60: 267-286
81 DeRuiter MC, Poelmann RE, VanMunsteren JC, Mironov V, Markwald RR, Gittenberger-de Groot AC. Embryonic endothelial cells transdifferentiate into mesenchymal cells expressing smooth muscle actins in vivo and in vitro. Circ Res 1997; 80 (04) 444-451
82 Rajantie I, Ilmonen M, Alminaite A, Ozerdem U, Alitalo K, Salven P. Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cells. Blood 2004; 104 (07) 2084-2086
83 Hirschi KK, D'Amore PA. Pericytes in the microvasculature. Cardiovasc Res 1996; 32 (04) 687-698
84 da Silva Meirelles L, Caplan AI, Nardi NB. In search of the in vivo identity of mesenchymal stem cells. Stem Cells 2008; 26 (09) 2287-2299
85 Ribatti D, Nico B, Crivellato E. The role of pericytes in angiogenesis. Int J Dev Biol 2011; 55 (03) 261-268
86 Krueger M, Bechmann I. CNS pericytes: concepts, misconceptions, and a way out. Glia 2010; 58 (01) 1-10
87 Nakagawa S, Deli MA, Nakao S. et al. Pericytes from brain microvessels strengthen the barrier integrity in primary cultures of rat brain endothelial cells. Cell Mol Neurobiol 2007; 27 (06) 687-694
88 Fisher M. Pericyte signaling in the neurovascular unit. Stroke 2009; 40 (3, Suppl): S13-S15
89 Tu Z, Li Y, Smith DS. et al. Retinal pericytes inhibit activated T cell proliferation. Invest Ophthalmol Vis Sci 2011; 52 (12) 9005-9010
90 Kim JA, Tran ND, Li Z, Yang F, Zhou W, Fisher MJ. Brain endothelial hemostasis regulation by pericytes. J Cereb Blood Flow Metab 2006; 26 (02) 209-217
91 Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer 2003; 3 (06) 401-410
92 Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J. Vascular-specific growth factors and blood vessel formation. Nature 2000; 407 (6801): 242-248
93 Eliasberg CD, Dar A, Jensen AR. et al. Perivascular stem cells diminish muscle atrophy following massive rotator cuff tears in a small animal model. J Bone Joint Surg Am 2017; 99 (04) 331-341
94 Chen CW, Montelatici E, Crisan M. et al. Perivascular multi-lineage progenitor cells in human organs: regenerative units, cytokine sources or both?. Cytokine Growth Factor Rev 2009; 20 (5-6): 429-434
95 Kida Y, Duffield JS. Pivotal role of pericytes in kidney fibrosis. Clin Exp Pharmacol Physiol 2011; 38 (07) 467-473
96 Dar A, Domev H, Ben-Yosef O. et al. Multipotent vasculogenic pericytes from human pluripotent stem cells promote recovery of murine ischemic limb. Circulation 2012; 125 (01) 87-99
97 König MA, Canepa DD, Cadosch D. et al. Direct transplantation of native pericytes from adipose tissue: a new perspective to stimulate healing in critical size bone defects. Cytotherapy 2016; 18 (01) 41-52
98 Mirzadeh Z, Merkle FT, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A. Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell 2008; 3 (03) 265-278
99 Mendel TA, Clabough EB, Kao DS. et al. Pericytes derived from adipose-derived stem cells protect against retinal vasculopathy. PLoS One 2013; 8 (05) e65691
100 Yu J, Vodyanik MA, Smuga-Otto K. et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 2007; 318 (5858): 1917-1920
101 Takahashi K, Tanabe K, Ohnuki M. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131 (05) 861-872
102 Madrid M, Sumen C, Aivio S, Saklayen N. Autologous induced pluripotent stem cell-based cell therapies: promise, progress, and challenges. Curr Protoc 2021; 1 (03) e88
103 Ilic D, Ogilvie C. Concise review: human embryonic stem cells - What have we done? What are we doing? Where are we going?. Stem Cells 2017; 35 (01) 17-25
104 Yamanaka S. Pluripotent stem cell-based cell therapy-promise and challenges. Cell Stem Cell 2020; 27 (04) 523-531
105 Damier P, Hirsch EC, Agid Y, Graybiel AM. The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson's disease. Brain 1999; 122 (Pt 8): 1437-1448
106 Oboudiyat C, Glazer H, Seifan A, Greer C, Isaacson RS. Alzheimer's disease. Semin Neurol 2013; 33 (04) 313-329
107 McColgan P, Tabrizi SJ. Huntington's disease: a clinical review. Eur J Neurol 2018; 25 (01) 24-34
108 Barker RA, Drouin-Ouellet J, Parmar M. Cell-based therapies for Parkinson disease—past insights and future potential. Nat Rev Neurol 2015; 11 (09) 492-503
109 Lindvall O, Rehncrona S, Brundin P. et al. Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up. Arch Neurol 1989; 46 (06) 615-631
110 Garitaonandia I, Gonzalez R, Sherman G, Semechkin A, Evans A, Kern R. Novel approach to stem cell therapy in Parkinson's disease. Stem Cells Dev 2018; 27 (14) 951-957
111 Accessed September 30, 2021 at: https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug
112 Essayan-Perez S, Zhou B, Nabet AM, Wernig M, Huang YA. Modeling Alzheimer's disease with human iPS cells: advancements, lessons, and applications. Neurobiol Dis 2019; 130: 104503
113 Hu W, Qiu B, Guan W. et al. Direct conversion of normal and Alzheimer's disease human fibroblasts into neuronal cells by small molecules. Cell Stem Cell 2015; 17 (02) 204-212
114 Mertens J, Paquola ACM, Ku M. et al. Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell Stem Cell 2015; 17 (06) 705-718
115 Kim S, Chang KA, Kim Ja. et al. The preventive and therapeutic effects of intravenous human adipose-derived stem cells in Alzheimer's disease mice. PLoS One 2012; 7 (09) e45757
116 Fang Y, Gao T, Zhang B, Pu J. Recent advances: decoding Alzheimer's disease with stem cells. Front Aging Neurosci 2018; 10: 77
117 The Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993; 72 (06) 971-983
118 Yoon Y, Kim HS, Jeon I. et al. Implantation of the clinical-grade human neural stem cell line, CTX0E03, rescues the behavioral and pathological deficits in the quinolinic acid-lesioned rodent model of Huntington's disease. Stem Cells 2020; 38 (08) 936-947
119 SC4HD Consortium. Stem cells for Huntington's disease (SC4HD): an international consortium to facilitate stem cell-based therapy for Huntington's disease. J Huntingtons Dis 2021; 10 (02) 221-226
120 Victor MB, Richner M, Hermanstyne TO. et al. Generation of human striatal neurons by microRNA-dependent direct conversion of fibroblasts. Neuron 2014; 84 (02) 311-323
121 Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 2002; 8 (09) 963-970
122 Marei HE, Hasan A, Rizzi R. et al. Potential of stem cell-based therapy for ischemic stroke. Front Neurol 2018; 9: 34
123 Polezhaev LV, Alexandrova MA, Vitvitsky VN, Girman SV, Golovina IL. Morphological, biochemical and physiological changes in brain nervous tissue of adult intact and hypoxia-subjected rats after transplantation of embryonic nervous tissue. J Hirnforsch 1985; 26 (03) 281-289
124 Huang W, Mo X, Qin C, Zheng J, Liang Z, Zhang C. Transplantation of differentiated bone marrow stromal cells promotes motor functional recovery in rats with stroke. Neurol Res 2013; 35 (03) 320-328
125 Tohill M, Mantovani C, Wiberg M, Terenghi G. Rat bone marrow mesenchymal stem cells express glial markers and stimulate nerve regeneration. Neurosci Lett 2004; 362 (03) 200-203
126 Steinberg GK, Kondziolka D, Bates D. SB623 Stroke Phase 1/2A Study Group. Response by Steinberg et al to letter regarding article, “clinical outcomes of transplanted modified bone marrow-derived mesenchymal stem cells in stroke: a Phase 1/2A study”. Stroke 2016; 47 (12) e269
127 Chen L, Zhang G, Khan AA, Guo X, Gu Y. Clinical efficacy and meta-analysis of stem cell therapies for patients with brain ischemia. Stem Cells Int 2016; 2016: 6129579
128 Curfman G. Stem cell therapy for heart failure: an unfulfilled promise?. JAMA 2019; 321 (12) 1186-1187
129 Nguyen PK, Rhee JW, Wu JC. Adult stem cell therapy and heart failure, 2000 to 2016: a systematic review. JAMA Cardiol 2016; 1 (07) 831-841
130 Hashimoto H, Olson EN, Bassel-Duby R. Therapeutic approaches for cardiac regeneration and repair. Nat Rev Cardiol 2018; 15 (10) 585-600
131 Jayaraj JS, Janapala RN, Qaseem A. et al. Efficacy and safety of stem cell therapy in advanced heart failure patients: a systematic review with a meta-analysis of recent trials between 2017 and 2019. Cureus 2019; 11 (09) e5585
132 Bani Hamad FR, Rahat N, Shankar K, Tsouklidis N. Efficacy of stem cell application in diabetes mellitus: promising future therapy for diabetes and its complications. Cureus 2021; 13 (02) e13563
133 de Klerk E, Hebrok M. Stem cell-based clinical trials for diabetes mellitus. Front Endocrinol (Lausanne) 2021; 12: 631463
134 Thakkar UG, Trivedi HL, Vanikar AV, Dave SD. Insulin-secreting adipose-derived mesenchymal stromal cells with bone marrow-derived hematopoietic stem cells from autologous and allogenic sources for type 1 diabetes mellitus. Cytotherapy 2015; 17 (07) 940-947
135 Rezania A, Bruin JE, Arora P. et al. Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat Biotechnol 2014; 32 (11) 1121-1133
136 Chen S, Du K, Zou C. Current progress in stem cell therapy for type 1 diabetes mellitus. Stem Cell Res Ther 2020; 11 (01) 275
137 Farber A, Eberhardt RT. The current state of critical limb ischemia: a systematic review. JAMA Surg 2016; 151 (11) 1070-1077
138 Parikh PP, Liu ZJ, Velazquez OC. A molecular and clinical review of stem cell therapy in critical limb ischemia. Stem Cells Int 2017; 2017: 3750829
139 Raval Z, Losordo DW. Cell therapy of peripheral arterial disease: from experimental findings to clinical trials. Circ Res 2013; 112 (09) 1288-1302
140 Samura M, Hosoyama T, Takeuchi Y, Ueno K, Morikage N, Hamano K. Therapeutic strategies for cell-based neovascularization in critical limb ischemia. J Transl Med 2017; 15 (01) 49
141 Tateno K, Minamino T, Toko H. et al. Critical roles of muscle-secreted angiogenic factors in therapeutic neovascularization. Circ Res 2006; 98 (09) 1194-1202
142 Xie B, Luo H, Zhang Y, Wang Q, Zhou C, Xu D. Autologous stem cell therapy in critical limb ischemia: a meta-analysis of randomized controlled trials. Stem Cells Int 2018; 2018: 7528464
143 Zafari N, Churilov L, MacIsaac RJ. et al. Diagnostic performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at estimating glomerular filtration rate in adults with diabetes mellitus: a systematic review and meta-analysis protocol. BMJ Open 2019; 9 (08) e031558
144 Chen TK, Knicely DH, Grams ME. Chronic kidney disease diagnosis and management: a review. JAMA 2019; 322 (13) 1294-1304
145 Stenvinkel P, Wadström J, Bertram T. et al. Implantation of autologous selected renal cells in diabetic chronic kidney disease stages 3 and 4 - clinical experience of a “first in human” study. Kidney Int Rep 2016; 1 (03) 105-113
146 Ludlow JW, Kelley RW, Bertram TA. The future of regenerative medicine: urinary system. Tissue Eng Part B Rev 2012; 18 (03) 218-224
147 Little MH, Kairath P. Regenerative medicine in kidney disease. Kidney Int 2016; 90 (02) 289-299
148 Griffin TP, Martin WP, Islam N, O'Brien T, Griffin MD. The promise of mesenchymal stem cell therapy for diabetic kidney disease. Curr Diab Rep 2016; 16 (05) 42
149 Shi Y, Wang Y, Li Q. et al. Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases. Nat Rev Nephrol 2018; 14 (08) 493-507
150 Hickson LJ, Abedalqader T, Ben-Bernard G. et al. A systematic review and meta-analysis of cell-based interventions in experimental diabetic kidney disease. Stem Cells Transl Med 2021; 10 (09) 1304-1319
151 Grange C, Skovronova R, Marabese F, Bussolati B. Stem cell-derived extracellular vesicles and kidney regeneration. Cells 2019; 8 (10) E1240
152 Ng NN, Thakor AS. Locoregional delivery of stem cell-based therapies. Sci Transl Med 2020; 12 (547) eaba4564
153 Fischer UM, Harting MT, Jimenez F. et al. Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect. Stem Cells Dev 2009; 18 (05) 683-692
154 Zhao L, Chen S, Shi X, Cao H, Li L. A pooled analysis of mesenchymal stem cell-based therapy for liver disease. Stem Cell Res Ther 2018; 9 (01) 72
155 Guzman R, De Los Angeles A, Cheshier S. et al. Intracarotid injection of fluorescence activated cell-sorted CD49d-positive neural stem cells improves targeted cell delivery and behavior after stroke in a mouse stroke model. Stroke 2008; 39 (04) 1300-1306
156 Li L, Jiang Q, Ding G. et al. Effects of administration route on migration and distribution of neural progenitor cells transplanted into rats with focal cerebral ischemia, an MRI study. J Cereb Blood Flow Metab 2010; 30 (03) 653-662
157 Kamiya N, Ueda M, Igarashi H. et al. Intra-arterial transplantation of bone marrow mononuclear cells immediately after reperfusion decreases brain injury after focal ischemia in rats. Life Sci 2008; 83 (11-12): 433-437
158 Misra V, Ritchie MM, Stone LL, Low WC, Janardhan V. Stem cell therapy in ischemic stroke: role of IV and intra-arterial therapy. Neurology 2012; 79 (13, Suppl 1): S207-S212
159 Moreira RdeC, Haddad AF, Silva SA. et al. Intracoronary stem-cell injection after myocardial infarction: microcirculation sub-study. Arq Bras Cardiol 2011; 97 (05) 420-426
160 Zaw Thin M, Ogunlade O, Comenge J. et al. Stem cell delivery to kidney via minimally invasive ultrasound-guided renal artery injection in mice. Sci Rep 2020; 10 (01) 7514
161 Regmi S, Pathak S, Thanh TP. et al. Intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against GalN/LPS-induced fulminant hepatic toxicity. Stem Cell Res Ther 2019; 10 (01) 230
162 Sang JF, Shi XL, Han B. et al. Intraportal mesenchymal stem cell transplantation prevents acute liver failure through promoting cell proliferation and inhibiting apoptosis. Hepatobiliary Pancreat Dis Int 2016; 15 (06) 602-611
163 Sasaki R, Takami T, Fujisawa K. et al. Trans-portal hepatic infusion of cultured bone marrow-derived mesenchymal stem cells in a steatohepatitis murine model. J Clin Biochem Nutr 2020; 67 (03) 274-282
164 Hare JM, DiFede DL, Rieger AC. et al. Randomized comparison of allogeneic versus autologous mesenchymal stem cells for nonischemic dilated cardiomyopathy: POSEIDON-DCM trial. J Am Coll Cardiol 2017; 69 (05) 526-537
165 Stavas J, Diaz-Gonzalez de Ferris M, Johns A, Jain D, Bertram T. Protocol and baseline data on renal autologous cell therapy injection in adults with chronic kidney disease secondary to congenital anomalies of the kidney and urinary tract. Blood Purif 2021; 50 (4-5): 678-683
166 A Study of Renal Autologous Cell Therapy™ (REACT) in Type 2 Diabetics with Chronic Kidney Disease. Accessed September 30, 2021 at: https://ClinicalTrials.gov/show/NCT02836574
167 Risk Evaluation and Mitigation Strategies. Accessed September 30, 2021 at: https://wwwfdagov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems
168 Biologics Application Process. Accessed September 30, 2021 at: https://wwwfdagov/vaccines-blood-biologics/development-approval-process-cber/biologics-license-applications-bla-process-cber