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Induced Pluripotent Stem Cells (iPSC)-derived Mesenchymal Stem Cells (MSCs) Showed Comparable Effects in Repair of Acute Kidney Injury as Compared to Adult MSCs

Xiaowu Huang, Huanhuan Wang, Yong Xu
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Abstract

Purpose: The study aimed to compare the therapeutic effects of iPSC-derived MSCs (iPSC-MSCs) and adult MSCs for acute kidney injury (AKI) therapy.

Materials and Methods: Model rats with ischemia/reperfusion (I/R)-induced AKI were randomly divided into three groups (n=15 for each group) to receive transplantation of iPSC-MSCs, adult MSCs, or the saline control. After transplantation, engraftment and differentiation of both iPSC-MSCs and adult MSCs were detected in the transplanted sites. Serum creatinine and blood urea nitrogen (BUN) for renal function evaluation were measured, and histological assays were performed as well.

Results: Compared with the saline control, both iPSC-MSCs and adult MSCs significantly (p<0.05 or 0.01) improved the renal function. Furthermore, iPSC-MSCs showed comparable effects in ameliorating tissue damage, reducing cell apoptosis and promoting vascularization with adult MSCs.

Conclusion: This study compared the therapeutic effects of iPSC-MSCs and adult MSCs for AKI treatment. Both iPSC-MSCs and adult MSCs were observed with comparable effects in repair of AKI. The results indicated that iPSC-MSCs may serve as an alternative source of MSCs for stem cell-based therapy for AKI therapy.


Keywords

acute kidney injury; induced pluripotent stem cells; mesenchymal stem cells; paracrine effects; stem cell-based therapy

References

Bonventre, J.V. & Weinberg, J.M. Recent advances in the pathophysiology of ischemic acute renal failure. J Am Soc Nephrol .2003;14(8):2199-2210.

Kellum, J.A., Bellomo, R. & Ronco, C. Definition and classification of acute kidney injury. Nephron Clin Pract .2008;109(4):c182-187.

Herrera, M.B., et al. Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury. Int J Mol Med .2004;14(6):1035-1041.

Morigi, M., et al. Human bone marrow mesenchymal stem cells accelerate recovery of acute renal injury and prolong survival in mice. Stem Cells.2008; 26(8):2075-2082.

Morigi, M., et al. Life-sparing effect of human cord blood-mesenchymal stem cells in experimental acute kidney injury. Stem Cells . 2010;28(3):513-522.

Qi, S. & Wu, D. Bone marrow-derived mesenchymal stem cells protect against cisplatin-induced acute kidney injury in rats by inhibiting cell apoptosis. Int J Mol Med.2013;32(6):1262-1272.

Lange, C., et al. Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute renal failure in rats. Kidney Int .2005;68(4):1613-1617.

Togel, F., et al. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol .2005;289(1):F31-42.

Zhuo, W., et al. Mesenchymal stem cells ameliorate ischemia-reperfusion-induced renal dysfunction by improving the antioxidant/oxidant balance in the ischemic kidney. Urol Int .2010;86(2):191-196.

Chen, Y.T., et al. Adipose-derived mesenchymal stem cell protects kidneys against ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction. J Transl Med .2011;9:51.

Gnecchi, M., et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med .2005;11(4):367-368.

Rubina, K., et al. Adipose stromal cells stimulate angiogenesis via promoting progenitor cell differentiation, secretion of angiogenic factors, and enhancing vessel maturation. Tissue Eng Part A. 2009;15(8):2039-2050.

Verseijden, F., et al. Angiogenic capacity of human adipose-derived stromal cells during adipogenic differentiation: an in vitro study. Tissue Eng Part A .2009;15(2):445-452.

Parekkadan, B. & Milwid, J.M. Mesenchymal stem cells as therapeutics. Annual review of biomedical engineering .2010;12:87-117.

Kretlow, J.D., et al. Donor age and cell passage affects differentiation potential of murine bone marrow-derived stem cells. BMC cell biology .2008;9:60.

Wagner, W., et al. Aging and replicative senescence have related effects on human stem and progenitor cells. PloS one .2009;4(6):e5846.

Katsara, O., et al. Effects of donor age, gender, and in vitro cellular aging on the phenotypic, functional, and molecular characteristics of mouse bone marrow-derived mesenchymal stem cells. Stem cells and development .2011;20(9):1549-1561.

Heeschen, C., et al. Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation .2004;109(13):1615-1622.

Roobrouck, V.D., Ulloa-Montoya, F. & Verfaillie, C.M. Self-renewal and differentiation capacity of young and aged stem cells. Experimental cell research .2008;314(9):1937-1944.

Xin, Y., et al. Aging adversely impacts biological properties of human bone marrow-derived mesenchymal stem cells: implications for tissue engineering heart valve construction. Artificial organs .2010;34(3):215-222.

Takahashi, K., et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell .2007;131(5): 861-872.

Yu, J., et al. Induced pluripotent stem cell lines derived from human somatic cells. Science .2007;318(5858):1917-1920.

Jung, Y., Bauer, G. & Nolta, J.A. Concise review: Induced pluripotent stem cell-derived mesenchymal stem cells: progress toward safe clinical products. Stem Cells .2012;30(1):42-47.

Lian, Q., et al. Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice. Circulation .2010;121(9):1113-1123.

Zuk, P.A., et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell.2002;13(12):4279-4295.

Xu, Y., Shi, T., Xu, A. & Zhang, L. 3D spheroid culture enhances survival and therapeutic capacities of MSCs injected into ischemic kidney. J Cell Mol Med .2016;20(7):1203-1213.

Okita, K., Nakagawa, M., Hyenjong, H., Ichisaka, T. & Yamanaka, S. Generation of mouse induced pluripotent stem cells without viral vectors. Science .2008(5903);322:949-953.

Yu, J., et al. Human induced pluripotent stem cells free of vector and transgene sequences. Science.2009; 324(5928):797-801.

Kim, D., et al. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell stem cell.2009; 4(6):472-476.




DOI: http://dx.doi.org/10.22037/uj.v0i0.5362

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