Human embryonic mesenchymal stem cells participate in differentiation of renal tubular cells in newborn mice

Yuan,Li; Liu,Hou‑Qi; Wu,Min‑Juan

doi:10.3892/etm.2016.3383

Human embryonic mesenchymal stem cells participate in differentiation of renal tubular cells in newborn mice

Authors:
- Li Yuan
- Hou‑Qi Liu
- Min‑Juan Wu
View Affiliations

Affiliations: Department of Nephrology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Histology and Embryology, Research Center of Developmental Biology, Second Military Medical University, Shanghai 200433, P.R. China
Published online on: May 24, 2016 https://doi.org/10.3892/etm.2016.3383
Pages: 641-648
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Stem cells are used with increasing success in the treatment of renal tubular injury. However, whether mesenchymal stem cells (MSC) differentiate into renal tubular epithelial cells remains controversial. The aims of the present study were to observe the localization of human embryonic MSCs (hMSCs) in the kidneys of newborn mice, and to investigate hMSC differentiation into tubular epithelium. Primary culture hMSCs were derived from 4‑7‑week‑old embryos and labeled with the cell membrane fluorescent dye PKH‑26. The degree of apoptosis, cell growth, differentiation and localization of hMSCs with and without this label were then determined using immunohistochemical methods and ﬂow cytometry. hMSCs and PKH26‑labeled hMSCs were revealed to differentiate into chondrocytes and adipocytes, and were demonstrated to have similar proliferative capability. In the two cell types, the antigens CD34 and CD45, indicative of hematopoietic lineages, were not expressed; however, the expression of the mesenchymal markers CD29 and CD90 in MSCs, was significantly increased. During a 4‑week culture period, laser confocal microscopy revealed that PKH26‑labeled hMSCs in the kidneys of newborn mice gradually dispersed. Two weeks after the injection of the PKH26‑labeled cells, the percentage of PKH26‑labeled hMSCs localized to the renal tubules was 10±2.1%. In conclusion, PKH26 labeling has no effect on hMSC differentiation, proliferation and mesenchymal cell surface features, and hMSCs injected into the kidneys of newborn mice may transform to renal tubule epithelium.

View Figures

View References

1	Morigi M and Benigni A: Mesenchymal stem cells and kidney repair. Nephrol Dial Transplant. 28:788–793. View Article : Google Scholar : PubMed/NCBI
2	Imai E and Iwatani H: The continuing story of renal repair with stem cells. J Am Soc Nephrol. 18:2423–2424. 2007. View Article : Google Scholar : PubMed/NCBI
3	Yuan L, Wu MJ, Sun HY, Xiong J, Zhang Y, Liu CY, Fu LL, Liu DM, Liu HQ and Mei CL: VEGF-modified human embryonic mesenchymal stem cell implantation enhances protection against cisplatin-induced acute kidney injury. Am J Physiol Renal Physiol. 300:F207–F218. 2011. View Article : Google Scholar : PubMed/NCBI
4	Selby NM, Crowley L, Fluck RJ, Mcintyre CW, Monaghan J, Lawson N and Kolhe NV: Use of electronic results reporting to diagnose and monitor AKI in hospitalized patients. Clin J Am Soc Nephrol. 7:533–540. 2012. View Article : Google Scholar : PubMed/NCBI
5	Morigi M, Imberti B, Zoja C, Corna D, Tomasoni S, Abbate M, Rottoli D, Angioletti S, Benigni A, Perico N, et al: Mesenchymal stem cells are renotropic, helping to repair the kidney and improve function in acute renal failure. J Am Soc Nephrol. 15:1794–1804. 2004. View Article : Google Scholar : PubMed/NCBI
6	Bussolati B, Hauser PV, Carvalhosa R and Camussi G: Contribution of stem cells to kidney repair. Curr Stem Cell Res Ther. 4:2–8. 2009. View Article : Google Scholar : PubMed/NCBI
7	Chhabra P and Brayman KL: The use of stem cells in kidney disease. Curr Opin Organ Transplant. 14:72–78. 2009. View Article : Google Scholar : PubMed/NCBI
8	Yokote S, Yamanaka S and Yokoo T: De novo kidney regeneration with stem cells. J Biomed Biotechnol. 2012:4535192012. View Article : Google Scholar : PubMed/NCBI
9	Hwang JH, Shim SS, Seok OS, Lee HY, Woo SK, Kim BH, Song HR, Lee JK and Park YK: Comparison of cytokine expression in mesenchymal stem cells from human placenta, cord blood, and bone marrow. J Korean Med Sci. 24:547–554. 2009. View Article : Google Scholar : PubMed/NCBI
10	Cao H, Heazlewood SY, Williams B, Cardozo D, Nigro J, Oteiza A and Nilsson SK: The role of CD44 in fetal and adult hematopoietic stem cell regulation. Haematologica. 101:26–37. 2016. View Article : Google Scholar : PubMed/NCBI
11	Gotherstrom C, Ringden O, Westgren M, Tammik C and Le Blanc K: Immunomodulatory effects of human foetal liver-derived mesenchymal stem cells. Bone Marrow Transplant. 32:265–272. 2003. View Article : Google Scholar : PubMed/NCBI
12	Li O, Tormin A, Sundberg B, Hyllner J, Le Blanc K and Scheding S: Human embryonic stem cell-derived mesenchymal stroma cells (hES-MSCs) engraft in vivo and support hematopoiesis without suppressing immune function: Implications for off-the shelf ES-MSC therapies. PLoS One. 8:e553192013. View Article : Google Scholar : PubMed/NCBI
13	O'Donoghue K and Fisk NM: Fetal stem cells. Best Pract Res Clin Obstet Gynaecol. 18:853–875. 2004. View Article : Google Scholar : PubMed/NCBI
14	Le Blanc K: Immunomodulatory effects of fetal and adult mesenchymal stem cells. Cytotherapy. 5:485–489. 2003. View Article : Google Scholar : PubMed/NCBI
15	Le Blanc K, Tammik L, Sundberg B, Haynesworth SE and Ringden O: Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol. 57:11–20. 2003. View Article : Google Scholar : PubMed/NCBI
16	Emanueli C, Lako M, Stojkovic M and Madeddu P: In search of the best candidate for regeneration of ischemic tissues: Are embryonic/fetal stem cells more advantageous than adult counterparts? Thromb Haemost. 94:738–749. 2005.PubMed/NCBI
17	Wu M, Yang L, Liu S, Li H, Hui N, Wang F and Liu H: Differentiation potential of human embryonic mesenchymal stem cells for skin-related tissue. Br J Dermatol. 155:282–291. 2006. View Article : Google Scholar : PubMed/NCBI
18	Institute of Laboratory Animal Resources (US). Committee on Care, Use of Laboratory Animals, and National Institutes of Health (US). Division of Research Resources: Guide for the care and use of laboratory animals (8th). National Academies Press. (Washington, DC). 2011.
19	Schimke MM, Marozin S and Lepperdinger G: Patient-specific age: The other side of the coin in advanced mesenchymal stem cell therapy. Front Physiol. 6:3622005.
20	Sterneckert JL, Reinhardt P and Scholer HR: Investigating human disease using stem cell models. Nat Rev Genet. 15:625–639. 2014. View Article : Google Scholar : PubMed/NCBI
21	Allers C, Lasala GP and Minguell JJ: Presence of osteoclast precursor cells during ex vivo expansion of bone marrow-derived mesenchymal stem cells for autologous use in cell therapy. Cytotherapy. 16:454–459. 2013. View Article : Google Scholar : PubMed/NCBI
22	Semon JA, Maness C, Zhang X, Sharkey SA, Beuttler MM, Shah FS, Pandey AC, Gimble JM, Zhang S, Scruggs BA, et al: Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis. Stem Cell Res Ther. 5:22014. View Article : Google Scholar : PubMed/NCBI
23	Barry FP and Murphy JM: Mesenchymal stem cells: Clinical applications and biological characterization. Int J Biochem Cell Biol. 36:568–584. 2004. View Article : Google Scholar : PubMed/NCBI
24	Zhang ZY, Teoh SH, Chong MS, Schantz JT, Fisk NM, Choolani MA and Chan J: Superior osteogenic capacity for bone tissue engineering of fetal compared with perinatal and adult mesenchymal stem cells. Stem Cells. 27:126–137. 2009. View Article : Google Scholar : PubMed/NCBI
25	Kawaguchi K, Katsuyama Y, Kikkawa S, Setsu T and Terashima T: PKH26 is an excellent retrograde and anterograde fluorescent tracer characterized by a small injection site and strong fluorescence emission. Arch Histol Cytol. 73:65–72. 2010. View Article : Google Scholar : PubMed/NCBI
26	Gallagher SJ, Shank JA, Bochner BS and Wagner EM: Methods to track leukocyte and erythrocyte transit through the bronchial vasculature in sheep. J Immunol Methods. 271:89–97. 2002. View Article : Google Scholar : PubMed/NCBI
27	Ude CC, Shamsul BS, Ng MH, Chen HC, Norhamdan MY, Aminuddin BS and Ruszymah BH: Bone marrow and adipose stem cells can be tracked with PKH26 until post staining passage 6 in in vitro and in vivo. Tissue Cell. 44:156–163. 2012. View Article : Google Scholar : PubMed/NCBI
28	Shao-Fang Z, Hong-Tian Z, Zhi-Nian Z and Yuan-Li H: PKH26 as a fluorescent label for live human umbilical mesenchymal stem cells. In Vitro Cell Dev Biol Anim. 47:516–520. 2011. View Article : Google Scholar : PubMed/NCBI
29	Haas SJ, Bauer P, Rolfs A and Wree A: Immunocytochemical characterization of in vitro PKH26-labelled and intracerebrally transplanted neonatal cells. Acta Histochem. 102:273–280. 2000. View Article : Google Scholar : PubMed/NCBI
30	Fox IJ, Daley GQ, Goldman SA, Huard J, Kamp TJ and Trucco M: Stem cell therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease. Science. 345:12473912014. View Article : Google Scholar : PubMed/NCBI
31	Pan Q, Qin X, Ma S, Wang H, Cheng K, Song X, Gao H, Wang Q, Tao R, Wang Y, et al: Myocardial protective effect of extracellular superoxide dismutase gene modified bone marrow mesenchymal stromal cells on infarcted mice hearts. Theranostics. 4:475–486. 2014. View Article : Google Scholar : PubMed/NCBI
32	Rashid ST and Vallier L: Induced pluripotent stem cells-alchemist's tale or clinical reality? Expert Rev Mol Med. 12:252010. View Article : Google Scholar : PubMed/NCBI
33	Togel F, Hu Z, Weiss K, Isaac J, Lange C and Westenfelder C: Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol. 289:F31–F42. 2005. View Article : Google Scholar : PubMed/NCBI
34	Semedo P, Palasio CG, Oliveira CD, Feitoza CQ, Gonçalves GM, Cenedeze MA, Wang PM, Teixeira VP, Reis MA, Pacheco-Silva A and Câmara NO: Early modulation of inflammation by mesenchymal stem cell after acute kidney injury. Int Immunopharmacol. 9:677–682. 2009. View Article : Google Scholar : PubMed/NCBI
35	Gatti S, Bruno S, Deregibus MC, Sordi A, Cantaluppi V, Tetta C and Camussi G: Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. Nephrol Dial Transplant. 26:1474–1483. 2011. View Article : Google Scholar : PubMed/NCBI
36	Bruno S, Grange C, Deregibus MC, Calogero RA, Saviozzi S, Collino F, Morando L, Busca A, Falda M, Bussolati B, et al: Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. J Am Soc Nephrol. 20:1053–1067. 2009. View Article : Google Scholar : PubMed/NCBI
37	Poulsom R, Forbes SJ, Hodivala-Dilke K, Ryan E, Wyles S, Navaratnarasah S, Jeffery R, Hunt T, Alison M, Cook T, et al: Bone marrow contributes to renal parenchymal turnover and regeneration. J Pathol. 195:229–235. 2001. View Article : Google Scholar : PubMed/NCBI
38	Gupta S, Verfaillie C, Chmielewski D, Kim Y and Rosenberg ME: A role for extrarenal cells in the regeneration following acute renal failure. Kidney Int. 62:1285–1290. 2002. View Article : Google Scholar : PubMed/NCBI
39	Broekema M, Harmsen MC, Koerts JA, Petersen AH, van Luyn MJ, Navis G and Popa ER: Determinants of tubular bone marrow-derived cell engraftment after renal ischemia/reperfusion in rats. Kidney Int. 68:2572–2581. 2005. View Article : Google Scholar : PubMed/NCBI
40	Lin F, Moran A and Igarashi P: Intrarenal cells, not bone marrow-derived cells, are the major source for regeneration in postischemic kidney. J Clin Invest. 115:1756–1764. 2005. View Article : Google Scholar : PubMed/NCBI
41	Duffield JS, Park KM, Hsiao LL, Kelley VR, Scadden DT, Ichimura T and Bonventre JV: Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells. J Clin Invest. 115:1743–1755. 2005. View Article : Google Scholar : PubMed/NCBI
42	Duffield JS and Bonventre JV: Kidney tubular epithelium is restored without replacement with bone marrow-derived cells during repair after ischemic injury. Kidney Int. 68:1956–1961. 2005. View Article : Google Scholar : PubMed/NCBI
43	Morigi M, Rota C, Montemurro T, Montelatici E, Lo Cicero V, Imberti B, Abbate M, Zoja C, Cassis P, Longaretti L, et al: Life-sparing effect of human cord blood-mesenchymal stem cells in experimental acute kidney injury. Stem Cells. 28:513–522. 2010.PubMed/NCBI
44	Sorokin L and Ekblom P: Development of tubular and glomerular cells of the kidney. Kidney Int. 41:657–664. 1992. View Article : Google Scholar : PubMed/NCBI
45	Narbaitz R, Vandorpe D and Levine DZ: Differentiation of renal intercalated cells in fetal and postnatal rats. Anat Embryol (Berl). 183:353–361. 1991. View Article : Google Scholar : PubMed/NCBI
46	Yokoo T, Ohashi T, Shen JS, Sakurai K, Miyazaki Y, Utsunomiya Y, Takahashi M, Terada Y, Eto Y, Kawamura T, et al: Human mesenchymal stem cells in rodent whole-embryo culture are reprogrammed to contribute to kidney tissues. Proc Natl Acad Sci USA. 102:3296–3300. 2005. View Article : Google Scholar : PubMed/NCBI
47	Herzog EL and Krause DS: Engraftment of marrow-derived epithelial cells: The role of fusion. Proc Am Thorac Soc. 3:691–695. 2006. View Article : Google Scholar : PubMed/NCBI
48	Fang TC, Alison MR, Cook HT, Jeffery R, Wright NA and Poulsom R: Proliferation of bone marrow-derived cells contributes to regeneration after folic acid-induced acute tubular injury. J Am Soc Nephrol. 16:1723–1732. 2005. View Article : Google Scholar : PubMed/NCBI
49	Yadav N, Rao S, Bhowmik DM and Mukhopadhyay A: Bone marrow cells contribute to tubular epithelium regeneration following acute kidney injury induced by mercuric chloride. Indian J Med Res. 136:211–220. 2012.PubMed/NCBI