Universal or Personalized Mesenchymal Stem Cell Therapies: Impact of Age, Sex, and Biological Source
Abstract
:1. Introduction
2. Impact of Age on the Immune System and MSCs
2.1. Aging of the Immune System
2.2. Aging of MSCs
3. Impact of Sex as a Biological Variable on the Immune System and MSCs
4. Impact of Biological Source on MSC Autoimmune Therapy
4.1. Osteoarthritis (OA)
4.1.1. Bone Marrow-Derived MSCs (BM-MSCs) in OA
4.1.2. Adipose-Derived MSCs (ASCs) in OA
4.1.3. Umbilical-Cord Derived MSCs (UMC-MSCs) in OA
4.2. Multiple Sclerosis
4.2.1. BM-MSCs in MS
4.2.2. ASCs in MS
4.2.3. UMC-MSCs in MS
4.3. Systemic Lupus Erythematosus (SLE)
4.3.1. BM-MSCs in SLE
4.3.2. ASCs in SLE
4.3.3. UMC-MSCs in SLE
4.4. Comparison of MSCs from Different Sources across Autoimmune Diseases
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Ankrum, J.A.; Ong, J.F.; Karp, J.M. Mesenchymal stem cells: Immune evasive, not immune privileged. Nat. Biotechnol. 2014, 32, 252–260. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Friedenstein, A.J.; Piatetzky, S., II; Petrakova, K.V. Osteogenesis in transplants of bone marrow cells. J. Embryol. Exp. Morphol. 1966, 16, 381–1390. [Google Scholar] [CrossRef] [PubMed]
- Dominici, M.; Le Blanc, K.; Mueller, I.; Slaper-Cortenbach, I.; Marini, F.C.; Krause, D.S.; Deans, R.J.; Keating, A.; Prockop, D.J.; Horwitz, E.M. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006, 8, 315–317. [Google Scholar] [CrossRef] [PubMed]
- Bernardo, M.E.; Fibbe, W.E. Mesenchymal stromal cells: Sensors and switchers of inflammation. Cell Stem Cell 2013, 13, 392–402. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nauta, A.J.; Fibbe, W.E. Immunomodulatory properties of mesenchymal stromal cells. Blood 2007, 110, 3499–3506. [Google Scholar] [CrossRef] [Green Version]
- Murphy, M.B.; Moncivais, K.; Caplan, A.I. Mesenchymal stem cells: Environmentally responsive therapeutics for regenerative medicine. Exp. Mol. Med. 2013, 45, e54. [Google Scholar] [CrossRef] [Green Version]
- Francois, M.; Romieu-Mourez, R.; Li, M.; Galipeau, J. Human MSC suppression correlates with cytokine induction of indoleamine 2,3-dioxygenase and bystander M2 macrophage differentiation. Mol. Ther. 2012, 20, 187–195. [Google Scholar] [CrossRef]
- Prockop, D.J. Concise review: Two negative feedback loops place mesenchymal stem/stromal cells at the center of early regulators of inflammation. Stem Cells 2013, 31, 2042–2046. [Google Scholar] [CrossRef]
- Collison, J. Autoimmunity: The ABCs of autoimmune disease. Nat. Rev. Rheumatol. 2018, 14, 248. [Google Scholar] [CrossRef]
- Rodríguez-Fuentes, D.E.; Fernández-Garza, L.E.; Samia-Meza, J.A.; Barrera-Barrera, S.A.; Caplan, A.I.; Barrera-Saldaña, H.A. Mesenchymal Stem Cells Current Clinical Applications: A Systematic Review. Arch. Med Res. 2020, 52, 93–101. [Google Scholar] [CrossRef]
- Le Blanc, K.; Tammik, C.; Rosendahl, K.; Zetterberg, E.; Ringden, O. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp. Hematol. 2003, 31, 890–896. [Google Scholar] [CrossRef]
- Galipeau, J.; Krampera, M.; Barrett, J.; Dazzi, F.; Deans, R.J.; DeBruijn, J.; Dominici, M.; Fibbe, W.E.; Gee, A.P.; Gimble, J.M.; et al. International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials. Cytotherapy 2015, 18, 151–159. [Google Scholar] [CrossRef] [Green Version]
- Ankrum, J.; Karp, J.M. Mesenchymal stem cell therapy: Two steps forward, one step back. Trends Mol. Med. 2010, 16, 203–209. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lalu, M.M.; McIntyre, L.; Pugliese, C.; Fergusson, D.; Winston, B.W.; Marshall, J.C.; Granton, J.; Stewart, D.J.; 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, e47559. [Google Scholar] [CrossRef]
- Aiello, A.; Farzaneh, F.; Candore, G.; Caruso, C.; Davinelli, S.; Gambino, C.M.; Ligotti, M.E.; Zareian, N.; Accardi, G. Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention. Front. Immunol. 2019, 10, 2247. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Simon, A.K.; Hollander, G.A.; McMichael, A. Evolution of the immune system in humans from infancy to old age. Proc. R. Soc. B Biol. Sci. 2015, 282, 20143085. [Google Scholar] [CrossRef]
- Diggs, J. Autoimmune Theory of Aging; Loue, S.J.D., Sajatovic, M., Eds.; Encyclopedia of Aging and Public Health; Springer: Boston, MA, USA, 2008; pp. 143–144. [Google Scholar]
- Chang, C. Neonatal autoimmune diseases. Lupus 2012, 21, 1487–1491. [Google Scholar] [CrossRef]
- Georgountzou, A.; Papadopoulos, N.G. Postnatal Innate Immune Development: From Birth to Adulthood. Front. Immunol. 2017, 8, 957. [Google Scholar] [CrossRef] [Green Version]
- Vadasz, Z.; Haj, T.; Kessel, A.; Toubi, E. Age-related autoimmunity. BMC Med. 2013, 11, 94. [Google Scholar] [CrossRef]
- Haynes, L. Aging of the Immune System: Research Challenges to Enhance the Health Span of Older Adults. Front. Aging 2020, 1, 602108. [Google Scholar] [CrossRef]
- Roura, S.; Farré, J.; Soler-Botija, C.; Llach, A.; Hove-Madsen, L.; Cairó, J.J.; Gòdia, F.; Cinca, J.; Bayes-Genis, A. Effect of aging on the pluripotential capacity of human CD105+ mesenchymal stem cells. Eur. J. Hear. Fail. 2006, 8, 555–563. [Google Scholar] [CrossRef]
- Stolzing, A.; Jones, E.; McGonagle, D.; Scutt, A. Age-related changes in human bone marrow-derived mesenchymal stem cells: Consequences for cell therapies. Mech. Ageing Dev. 2008, 129, 163–173. [Google Scholar] [CrossRef] [PubMed]
- Carvalho, M.S.; Alves, L.; Bogalho, I.; Cabral, J.M.S.; da Silva, C.L. Impact of Donor Age on the Osteogenic Supportive Capacity of Mesenchymal Stromal Cell-Derived Extracellular Matrix. Front. Cell Dev. Biol. 2021, 9, 747521. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.K.; Ogando, C.R.; Wang See, C.; Chang, T.Y.; Barabino, G.A. Changes in phenotype and differentiation potential of human mesenchymal stem cells aging in vitro. Stem Cell Res. Ther. 2018, 9, 131. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stenderup, K.; Justesen, J.; Clausen, C.; Kassem, M. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 2003, 33, 919–926. [Google Scholar] [CrossRef] [PubMed]
- Liu, M.; Lei, H.; Dong, P.; Fu, X.; Yang, Z.; Yang, Y.; Ma, J.; Liu, X.; Cao, Y.; Xiao, R. Adipose-Derived Mesenchymal Stem Cells from the Elderly Exhibit Decreased Migration and Differentiation Abilities with Senescent Properties. Cell Transplant. 2017, 26, 1505–1519. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Choudhery, M.S.; Badowski, M.; Muise, A.; Pierce, J.; Harris, D.T. Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation. J. Transl. Med. 2014, 12, 8. [Google Scholar] [CrossRef] [Green Version]
- Zhang, Y.; Ravikumar, M.; Ling, L.; Nurcombe, V.; Cool, S.M. Age-Related Changes in the Inflammatory Status of Human Mesenchymal Stem Cells: Implications for Cell Therapy. Stem Cell Rep. 2021, 16, 694–707. [Google Scholar] [CrossRef]
- Lasry, A.; Ben-Neriah, Y. Senescence-associated inflammatory responses: Aging and cancer perspectives. Trends Immunol. 2015, 36, 217–228. [Google Scholar] [CrossRef]
- Gugliandolo, A.; Bramanti, P.; Mazzon, E. Mesenchymal Stem Cells in Multiple Sclerosis: Recent Evidence from Pre-Clinical to Clinical Studies. Int. J. Mol. Sci. 2020, 21, 8662. [Google Scholar] [CrossRef]
- Rivera, F.J.; de la Fuente, A.G.; Zhao, C.; Silva, M.E.; Gonzalez, G.A.; Wodnar, R.; Feichtner, M.; Lange, S.; Errea, O.; Priglinger, E.; et al. Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination. Glia 2019, 67, 1510–1525. [Google Scholar] [CrossRef] [PubMed]
- Efimenko, A.; Dzhoyashvili, N.; Kalinina, N.; Kochegura, T.; Akchurin, R.; Tkachuk, V.; Parfyonova, Y. Adipose-derived mesenchymal stromal cells from aged patients with coronary artery disease keep mesenchymal stromal cell properties but exhibit characteristics of aging and have impaired angiogenic potential. Stem Cells Transl. Med. 2013, 3, 32–41. [Google Scholar] [CrossRef] [PubMed]
- Shi, Y.Y.; Nacamuli, R.P.; Salim, A.; Longaker, M.T. The osteogenic potential of adipose-derived mesenchymal cells is maintained with aging. Plast. Reconstr. Surg. 2005, 116, 1686–1696. [Google Scholar] [CrossRef]
- Bouman, A.; Heineman, M.J.; Faas, M.M. Sex hormones and the immune response in humans. Hum. Reprod. Updat. 2005, 11, 411–423. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ghazeeri, G.; Abdullah, L.; Abbas, O. Immunological differences in women compared with men: Overview and contributing factors. Am. J. Reprod. Immunol. 2011, 66, 163–169. [Google Scholar] [CrossRef] [PubMed]
- Beery, A.K.; Zucker, I. Sex bias in neuroscience and biomedical research. Neurosci. Biobehav. Rev. 2011, 35, 565–572. [Google Scholar] [CrossRef] [Green Version]
- Voskuhl, R. Sex differences in autoimmune diseases. Biol. Sex Differ. 2011, 2, 1. [Google Scholar] [CrossRef] [Green Version]
- Fish, E.N. The X-files in immunity: Sex-based differences predispose immune responses. Nat. Rev. Immunol. 2008, 8, 737–744. [Google Scholar] [CrossRef]
- Liu, K.; Kurien, B.T.; Zimmerman, S.L.; Kaufman, K.M.; Taft, D.; Kottyan, L.; Lazaro, S.; Weaver, C.A.; Ice, J.A.; Adler, A.J.; et al. X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjogren’s Syndrome. Arthritis Rheumatol. 2015, 68, 1290–1300. [Google Scholar] [CrossRef]
- Shaw, T.M.; Zhang, W.; McCoy, S.S.; Pagenkopf, A.; Carp, D.M.; Garg, S.; Parker, M.H.; Qiu, X.; Scofield, R.H.; Galipeau, J.; et al. X-linked genes exhibit miR6891-5p-regulated skewing in Sjogren’s syndrome. J. Mol. Med. 2022, 1–3. [Google Scholar] [CrossRef]
- Zanotti, S.; Kalajzic, I.; Aguila, H.L.; Canalis, E. Sex and genetic factors determine osteoblastic differentiation potential of murine bone marrow stromal cells. PLoS ONE 2014, 9, e86757. [Google Scholar] [CrossRef] [Green Version]
- Strube, P.; Mehta, M.; Baerenwaldt, A.; Trippens, J.; Wilson, C.J.; Ode, A.; Perka, C.; Duda, G.N.; Kasper, G. Sex-specific compromised bone healing in female rats might be associated with a decrease in mesenchymal stem cell quantity. Bone 2009, 45, 1065–1072. [Google Scholar] [CrossRef] [PubMed]
- Ock, S.-A.; Lee, Y.-M.; Park, J.-S.; Shivakumar, S.B.; Moon, S.-W.; Sung, N.-J.; Lee, W.-J.; Jang, S.-J.; Park, J.-M.; Lee, S.-C.; et al. Evaluation of phenotypic, functional and molecular characteristics of porcine mesenchymal stromal/stem cells depending on donor age, gender and tissue source. J. Veter-Med Sci. 2016, 78, 987–995. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bianconi, E.; Casadei, R.; Frabetti, F.; Ventura, C.; Facchin, F.; Canaider, S. Sex-Specific Transcriptome Differences in Human Adipose Mesenchymal Stem Cells. Genes 2020, 11, 909. [Google Scholar] [CrossRef] [PubMed]
- Hwang, J.J.; Rim, Y.A.; Nam, Y.; Ju, J.H. Recent Developments in Clinical Applications of Mesenchymal Stem Cells in the Treatment of Rheumatoid Arthritis and Osteoarthritis. Front. Immunol. 2021, 12, 448. [Google Scholar] [CrossRef]
- Sen, R.; Hurley, J.A. Osteoarthritis. StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2022. [Google Scholar]
- Yang, X.; Chen, L.; Xu, X.; Li, C.; Huang, C.; Deng, C.-X. TGF-β/Smad3 Signals Repress Chondrocyte Hypertrophic Differentiation and Are Required for Maintaining Articular Cartilage. J. Cell Biol. 2001, 153, 35–46. [Google Scholar] [CrossRef] [Green Version]
- Loeser, R.F.; Goldring, S.R.; Scanzello, C.R.; Goldring, M.B. Osteoarthritis: A disease of the joint as an organ. Arthritis Rheum. 2012, 64, 1697–1707. [Google Scholar] [CrossRef] [Green Version]
- Koyama, T.; Uchida, K.; Fukushima, K.; Ohashi, Y.; Uchiyama, K.; Inoue, G.; Takahira, N.; Takaso, M. Elevated levels of TNF-α, IL-1β and IL-6 in the synovial tissue of patients with labral tear: A comparative study with hip osteoarthritis. BMC Musculoskelet. Disord. 2021, 22, 33. [Google Scholar] [CrossRef]
- Chen, Y.; Jiang, W.; Yong, H.; He, M.; Yang, Y.; Deng, Z.; Li, Y. Macrophages in osteoarthritis: Pathophysiology and therapeutics. Am. J. Transl. Res. 2020, 12, 261. [Google Scholar]
- Zhu, C.; Wu, W.; Qu, X. Mesenchymal stem cells in osteoarthritis therapy: A review. Am. J. Transl. Res. 2021, 13, 448–461. [Google Scholar]
- Murphy, J.M.; Dixon, K.; Beck, S.; Fabian, D.; Feldman, A.; Barry, F. Reduced chondrogenic and adipogenic activity of mesenchymal stem cells from patients with advanced osteoarthritis. Arthritis Care Res. 2002, 46, 704–713. [Google Scholar] [CrossRef] [PubMed]
- Cipriani, P.; Ruscitti, P.; Di Benedetto, P.; Carubbi, F.; Liakouli, V.; Berardicurti, O.; Ciccia, F.; Triolo, G.; Giacomelli, R. Mesenchymal stromal cells and rheumatic diseases: New tools from pathogenesis to regenerative therapies. Cytotherapy 2015, 17, 832–849. [Google Scholar] [CrossRef] [Green Version]
- Markov, A.; Thangavelu, L.; Aravindhan, S.; Zekiy, A.O.; Jarahian, M.; Chartrand, M.S.; Pathak, Y.; Marofi, F.; Shamlou, S.; Hassanzadeh, A. Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders. Stem Cell Res. Ther. 2021, 12, 192. [Google Scholar] [CrossRef] [PubMed]
- Shapiro, S.A.; Kazmerchak, S.E.; Heckman, M.G.; Zubair, A.C.; O’Connor, M.I. A Prospective, Single-Blind, Placebo-Controlled Trial of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis. Am. J. Sports Med. 2016, 45, 82–90. [Google Scholar] [CrossRef] [PubMed]
- Zhang, R.; Ma, J.; Han, J.; Zhang, W.; Ma, J. Mesenchymal stem cell related therapies for cartilage lesions and osteoarthritis. Am. J. Transl. Res. 2019, 11, 6275–6289. [Google Scholar]
- Chahal, J.; Gómez-Aristizábal, A.; Shestopaloff, K.; Bhatt, S.; Chaboureau, A.; Fazio, A.; Chisholm, J.; Weston, A.; Chiovitti, J.; Keating, A.; et al. Bone Marrow Mesenchymal Stromal Cell Treatment in Patients with Osteoarthritis Results in Overall Improvement in Pain and Symptoms and Reduces Synovial Inflammation. Stem Cells Transl. Med. 2019, 8, 746–757. [Google Scholar] [CrossRef] [Green Version]
- Damia, E.; Chicharro, D.; Lopez, S.; Cuervo, B.; Rubio, M.; Sopena, J.J.; Vilar, J.M.; Carrillo, J.M. Adipose-Derived Mesenchymal Stem Cells: Are They a Good Therapeutic Strategy for Osteoarthritis? Int. J. Mol. Sci. 2018, 19, 1926. [Google Scholar] [CrossRef] [Green Version]
- Pers, Y.-M.; Rackwitz, L.; Ferreira, R.; Pullig, O.; Delfour, C.; Barry, F.; Sensebe, L.; Casteilla, L.; Fleury, S.; Bourin, P.; et al. Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial. Stem Cells Transl. Med. 2016, 5, 847–856. [Google Scholar] [CrossRef] [Green Version]
- Berenbaum, F.; Grifka, J.; Cazzaniga, S.; D’Amato, M.; Giacovelli, G.; Chevalier, X.; Rannou, F.; Rovati, L.; Maheu, E. A randomised, double-blind, controlled trial comparing two intra-articular hyaluronic acid preparations differing by their molecular weight in symptomatic knee osteoarthritis. Ann. Rheum. Dis. 2012, 71, 1454–1460. [Google Scholar] [CrossRef]
- Jo, C.H.; Gil Lee, Y.; Shin, W.H.; Kim, H.; Chai, J.W.; Jeong, E.C.; Kim, J.E.; Shim, H.; Shin, J.S.; Shin, I.S.; et al. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: A proof-of-concept clinical trial. Stem Cells 2014, 32, 1254–1266. [Google Scholar] [CrossRef]
- Wang, Y.; Jin, W.; Liu, H.; Cui, Y.; Mao, Q.; Fei, Z.; Xiang, C. Curative Effect of Human Umbilical Cord Mesenchymal Stem Cells by Intra-Articular Injection for Degenerative Knee Osteoarthritis. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2016, 30, 1472–1477. [Google Scholar] [CrossRef] [PubMed]
- Matas, J.; Orrego, M.; Amenabar, D.; Infante, C.; Tapia-Limonchi, R.; Cadiz, M.I.; Alcayaga-Miranda, F.; González, P.L.; Muse, E.; Khoury, M.; et al. Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis: Repeated MSC Dosing Is Superior to a Single MSC Dose and to Hyaluronic Acid in a Controlled Randomized Phase I/II Trial. Stem Cells Transl. Med. 2019, 8, 215–224. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Garg, N.; Smith, T.W. An update on immunopathogenesis, diagnosis, and treatment of multiple sclerosis. Brain Behav. 2015, 5, e00362. [Google Scholar] [CrossRef] [PubMed]
- International Multiple Sclerosis Genetics Consorciaum (IMSGC); Hafler, D.A.; Compston, A.; Sawcer, S.; Lander, E.S.; Daly, M.J.; De Jager, P.L.; Bakker, P.I.W.D.; Gabriel, S.B.; Mirel, D.B.; et al. Risk alleles for multiple sclerosis identified by a genomewide study. N. Engl. J. Med. 2007, 357, 851–862. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Baecher-Allan, C.; Kaskow, B.J.; Weiner, H.L. Multiple Sclerosis: Mechanisms and Immunotherapy. Neuron 2018, 97, 742–768. [Google Scholar] [CrossRef] [Green Version]
- Dahbour, S.; Jamali, F.; Alhattab, D.; Al-Radaideh, A.; Ababneh, O.; Al-Ryalat, N.; Al Bdour, M.; Hourani, B.; Msallam, M.; Rasheed, M.; et al. Mesenchymal stem cells and conditioned media in the treatment of multiple sclerosis patients: Clinical, ophthalmological and radiological assessments of safety and efficacy. CNS Neurosci. Ther. 2017, 23, 866–874. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.; Ma, Y.; Du, B.; Wang, Y.; Yang, G.-Y.; Bi, X. Mesenchymal Stem Cells Attenuated Blood-Brain Barrier Disruption via Downregulation of Aquaporin-4 Expression in EAE Mice. Mol. Neurobiol. 2020, 57, 3891–3901. [Google Scholar] [CrossRef]
- Cedola, A.; Bravin, A.; Bukreeva, I.; Fratini, M.; Pacureanu, A.; Mittone, A.; Massimi, L.; Cloetens, P.; Coan, P.; Campi, G.; et al. X-Ray Phase Contrast Tomography Reveals Early Vascular Alterations and Neuronal Loss in a Multiple Sclerosis Model. Sci. Rep. 2017, 7, 5890. [Google Scholar] [CrossRef]
- Bai, L.; Lennon, D.P.; Eaton, V.; Maier, K.; Caplan, A.; Miller, S.D.; Miller, R.H. Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia 2009, 57, 1192–1203. [Google Scholar] [CrossRef] [Green Version]
- Shokati, A.; Naser Moghadasi, A.; Nikbakht, M.; Sahraian, M.A.; Mousavi, S.A.; Ai, J. A focus on allogeneic mesenchymal stromal cells as a versatile therapeutic tool for treating multiple sclerosis. Stem Cell Res. Ther. 2021, 12, 400. [Google Scholar] [CrossRef]
- Mohammadzadeh, A.; Pourfathollah, A.A.; Shahrokhi, S.; Fallah, A.; Tahoori, M.T.; Amari, A.; Forouzandeh, M.; Soleimani, M. Evaluation of AD-MSC (adipose-derived mesenchymal stem cells) as a vehicle for IFN-β delivery in experimental autoimmune encephalomyelitis. Clin. Immunol. 2016, 169, 98–106. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bravo, B.; Gallego, M.I.; Flores, A.I.; Bornstein, R.; Puente-Bedia, A.; Hernández, J.; de la Torre, P.; García-Zaragoza, E.; Perez-Tavarez, R.; Grande, J.; et al. Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis. Stem Cell Res. Ther. 2016, 7, 43. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fernández, O.; Izquierdo, G.; Fernández, V.; Leyva, L.; Reyes, V.; Guerrero, M.; León, A.; Arnaiz, C.; Navarro, G.; Páramo, M.D.; et al. Adipose-derived mesenchymal stem cells (AdMSC) for the treatment of secondary-progressive multiple sclerosis: A triple blinded, placebo controlled, randomized phase I/II safety and feasibility study. PLoS ONE 2018, 13, e0195891. [Google Scholar] [CrossRef] [Green Version]
- Kramer, P.R.; Kramer, S.F.; Guan, G. 17 beta-estradiol regulates cytokine release through modulation of CD16 expression in monocytes and monocyte-derived macrophages. Arthritis Care Res. 2004, 50, 1967–1975. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.-T.; Ting, C.-H.; Yen, M.-L.; Liu, K.-J.; Sytwu, H.-K.; Wu, K.K.; Yen, B.L. Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: Review of current clinical trials. J. Biomed. Sci. 2016, 23, 76. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, S.; Wang, J.; Han, R.; Meng, M.; Wang, W.; Zhao, Y.; Yang, F.; Yang, L.; Gao, H.; Zhao, Y.; et al. Therapeutic effect of transplanted umbilical cord mesenchymal stem cells in a cynomolgus monkey model of multiple sclerosis. Am. J. Transl. Res. 2019, 11, 2516–2531. [Google Scholar]
- Jagessar, S.A.; Holtman, I.R.; Hofman, S.; Morandi, E.; Heijmans, N.; Laman, J.D.; Gran, B.; Faber, B.W.; Van Kasteren, S.I.; Eggen, B.J.L.; et al. Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein. J. Immunol. 2016, 197, 1074–1088. [Google Scholar] [CrossRef] [Green Version]
- Li, J.-F.; Zhang, D.-J.; Geng, T.; Chen, L.; Huang, H.; Yin, H.-L.; Zhang, Y.-Z.; Lou, J.-Y.; Cao, B.; Wang, Y.-L. The potential of human umbilical cord-derived mesenchymal stem cells as a novel cellular therapy for multiple sclerosis. Cell Transplant. 2014, 23 (Suppl. 1), 113–122. [Google Scholar] [CrossRef]
- Meng, M.; Liu, Y.; Wang, W.; Wei, C.; Liu, F.; Du, Z.; Xie, Y.; Tang, W.; Hou, Z.; Li, Q. Umbilical cord mesenchymal stem cell transplantation in the treatment of multiple sclerosis. Am. J. Transl. Res. 2018, 10, 212–223. [Google Scholar]
- Rafieemehr, H.; Kheyrandish, M.; Soleimani, M. Neuroprotective Effects of Transplanted Mesenchymal Stromal Cells-derived Human Umbilical Cord Blood Neural Progenitor Cells in EAE. Iran. J. Allergy Asthma Immunol. 2015, 14, 596–604. [Google Scholar]
- Lai, N.S.; Koo, M.; Yu, C.L.; Lu, M.C. Immunopathogenesis of systemic lupus erythematosus and rheumatoid arthritis: The role of aberrant expression of non-coding RNAs in T cells. Clin. Exp. Immunol. 2017, 187, 327–336. [Google Scholar] [CrossRef] [Green Version]
- Fanouriakis, A.; Kostopoulou, M.; Alunno, A.; Aringer, M.; Bajema, I.; Boletis, J.N.; Cervera, R.; Doria, A.; Gordon, C.; Govoni, M.; et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann. Rheum. Dis. 2019, 78, 736–745. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fathollahi, A.; Gabalou, N.B.; Aslani, S. Mesenchymal stem cell transplantation in systemic lupus erythematous, a mesenchymal stem cell disorder. Lupus 2018, 27, 1053–1064. [Google Scholar] [CrossRef] [PubMed]
- Pan, L.; Lu, M.P.; Wang, J.H.; Xu, M.; Yang, S.R. Immunological pathogenesis and treatment of systemic lupus erythematosus. World J. Pediatr. 2019, 16, 19–30. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tsokos, G.C.; Lo, M.S.; Costa Reis, P.; Sullivan, K.E. New insights into the immunopathogenesis of systemic lupus erythematosus. Nat. Rev. Rheumatol. 2016, 12, 716–730. [Google Scholar] [CrossRef]
- Gu, Z.; Akiyama, K.; Ma, X.; Zhang, H.; Feng, X.; Yao, G.; Hou, Y.; Lu, L.; Gilkeson, G.; Silver, R.; et al. Transplantation of umbilical cord mesenchymal stem cells alleviates lupus nephritis in MRL/lpr mice. Lupus 2010, 19, 1502–1514. [Google Scholar] [CrossRef]
- Guimarães, P.M.; Scavuzzi, B.M.; Stadtlober, N.P.; Santos, L.F.D.R.F.; Lozovoy, M.A.B.; Iriyoda, T.M.V.; Costa, N.T.; Reiche, E.M.V.; Maes, M.; Dichi, I.; et al. Cytokines in systemic lupus erythematosus: Far beyond Th1/Th2 dualism lupus: Cytokine profiles. Immunol. Cell Biol. 2017, 95, 824–831. [Google Scholar] [CrossRef]
- Petri, M.; Bechtel, B.; Dennis, G.; Shah, M.; McLaughlin, T.; Kan, H.; Molta, C. Burden of corticosteroid use in patients with systemic lupus erythematosus: Results from a Delphi panel. Lupus 2014, 23, 1006–1013. [Google Scholar] [CrossRef]
- Tang, W.-Y.; Liu, J.-H.; Peng, C.-J.; Liao, Y.; Luo, J.-S.; Sun, X.; Tang, Y.-L.; Luo, X.-Q. Functional Characteristics and Application of Mesenchymal Stem Cells in Systemic Lupus Erythematosus. Arch. Immunol. Ther. Exp. 2021, 69, 7. [Google Scholar] [CrossRef]
- Li, W.; Chen, W.; Sun, L. An Update for Mesenchymal Stem Cell Therapy in Lupus Nephritis. Kidney Dis. 2021, 7, 79–89. [Google Scholar] [CrossRef]
- Sun, L.Y.; Zhang, H.Y.; Feng, X.B.; Hou, Y.Y.; Lu, L.W.; Fan, L.M. Abnormality of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus. Lupus 2007, 16, 121–128. [Google Scholar] [CrossRef] [PubMed]
- Carrion, F.; Nova, E.; Ruiz, C.; Diaz, F.; Inostroza, C.; Rojo, D.; Mönckeberg, G.; Figueroa, F. Autologous mesenchymal stem cell treatment increased T regulatory cells with no effect on disease activity in two systemic lupus erythematosus patients. Lupus 2009, 19, 317–322. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Wang, D.; Liang, J.; Zhang, H.; Sun, L. Mesenchymal SCT ameliorates refractory cytopenia in patients with systemic lupus erythematosus. Bone Marrow Transplant. 2012, 48, 544–550. [Google Scholar] [CrossRef] [PubMed]
- Park, M.J.; Kwok, S.K.; Lee, S.H.; Kim, E.K.; Park, S.H.; Cho, M.L. Adipose tissue-derived mesenchymal stem cells induce expansion of interleukin-10-producing regulatory B cells and ameliorate autoimmunity in a murine model of systemic lupus erythematosus. Cell Transplant. 2015, 24, 2367–2377. [Google Scholar] [CrossRef] [Green Version]
- Wang, D.; Huang, S.; Yuan, X.; Liang, J.; Xu, R.; Yao, G.; Feng, X.; Sun, L. The regulation of the Treg/Th17 balance by mesenchymal stem cells in human systemic lupus erythematosus. Cell. Mol. Immunol. 2015, 14, 423–431. [Google Scholar] [CrossRef] [Green Version]
- Qu, W.; Wang, Z.; Engelberg-Cook, E.; Yan, D.; Siddik, A.B.; Bu, G.; Allickson, J.G.; Kubrova, E.; Caplan, A.I.; Hare, J.M.; et al. Efficacy and Safety of MSC Cell Therapies for Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis. Stem Cells Transl. Med. 2022, 1–6. [Google Scholar] [CrossRef]
- Abu-El-Rub, E.; Khasawneh, R.R.; Almahasneh, F.; Altaany, Z.; Bataineh, N.; Zegallai, H.; Sekaran, S. Mesenchymal stem cells and COVID-19: What they do and what they can do. World J. Stem Cells 2021, 13, 1318–1337. [Google Scholar] [CrossRef]
Osteoarthritis | Multiple Sclerosis | Lupus | ||
---|---|---|---|---|
Bone-marrow-derived MSC | Effectiveness | Knee pain reduction | Reduce microgliosis and astrocytosis Increase BBB function Increased oligodendrocytes | Suppressed in vitro peripheral blood lymphocyte levels Improved blood cell count |
Biomarker | IL-12p40 decreases VEGF increases | IL-10 increased IL-4 increased IL-6 increase Glutathione increased IL-6 decreased IL-1ß decreased TNF-α decreased IL-12p70 decreased VEGF increase | Increased CD4+CD25+FoxP3+ cell counts Treg increased Th17 decreased | |
Adipose-derived MSC | Effectiveness | Strengthens joints Decreased WOMAC scores Increased synovial lining | Less effective Increased symptoms of urinary tract infections Temporarily increased severity of MS then decreased | Reduction of SLEDAI scores Lower than baseline of urine proteins Increased renal function |
Biomarker | VEGF increase TGF-ß secretion | IL-10 increased IL-4 increased IL-17 decrease Inhibited T-cell expansion | Breg ncreased Foxp3-expressing regulatory T cells increased | |
Umbilical-cord-derived MSC | Effectiveness | No reoccurring knee pain Decreased WOMAC scores | Demyelinated region did not decrease on MRI Promoted remyelination Clinical manifestations improved and less relapses Reduced astrogliosis | Improved renal function Reduction of SLEDAI scores |
Biomarker | IL-10 increased IL-4 increased IL-5 decreased TNF-α decreased IL-17 decrease HGF increase VEGF increases Decreased NK cells | MCP-1 decreased in mice Urine proteins decrease Treg increased Inhibited Th17 cells IL-17 decreased No changes in IL-6 nor IL-17A TNF-a decreased |
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Carp, D.M.; Liang, Y. Universal or Personalized Mesenchymal Stem Cell Therapies: Impact of Age, Sex, and Biological Source. Cells 2022, 11, 2077. https://doi.org/10.3390/cells11132077
Carp DM, Liang Y. Universal or Personalized Mesenchymal Stem Cell Therapies: Impact of Age, Sex, and Biological Source. Cells. 2022; 11(13):2077. https://doi.org/10.3390/cells11132077
Chicago/Turabian StyleCarp, Diana M., and Yun Liang. 2022. "Universal or Personalized Mesenchymal Stem Cell Therapies: Impact of Age, Sex, and Biological Source" Cells 11, no. 13: 2077. https://doi.org/10.3390/cells11132077