Autografting of bone marrow mesenchymal stem cells alleviates streptozotocin‑induced diabetes in miniature pigs: Real‑time tracing with MRI in vivo

Tang,Kuanxiao; Xiao,Xiaoyan; Liu,Dayue; Shen,Yunfeng; Chen,Yingming; Wang,Yu; Li,Baoying; Yu,Fei; Ma,Dedong; Yan,Jinhua; Liang,Hua; Yang,Daizhi; Weng,Jianping

doi:10.3892/ijmm.2014.1729

Autografting of bone marrow mesenchymal stem cells alleviates streptozotocin‑induced diabetes in miniature pigs: Real‑time tracing with MRI in vivo

Authors:
- Kuanxiao Tang
- Xiaoyan Xiao
- Dayue Liu
- Yunfeng Shen
- Yingming Chen
- Yu Wang
- Baoying Li
- Fei Yu
- Dedong Ma
- Jinhua Yan
- Hua Liang
- Daizhi Yang
- Jianping Weng
View Affiliations

Affiliations: Department of Endocrinology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China, Department of Nephrology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Vascular Surgery and Radiology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: April 7, 2014 https://doi.org/10.3892/ijmm.2014.1729
Pages: 1469-1476
Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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

Cellular replacement therapy for diabetes mellitus (DM) has received much attention. In this study, we investigated the effect of transplantation of autologous bone marrow‑derived mesenchymal stem cells (ABMSCs) in streptozotocin (STZ)‑induced diabetic miniature pigs. Miniature pig BMSCs were cultured, labeled with superparamagnetic iron oxide (SPIO) and transplanted into the pancreas of diabetic miniature pigs through targeted intervention. Blood glucose levels, intravenous and oral glucose tolerance test (OGTT), serum insulin, C‑peptide and islets histology were analyzed. These transplanted cells were then identified by magnetic resonance imaging (MRI). The results showed that transplantation of ABMSCs reversed STZ‑induced diabetes in miniature pigs. Blood glucose levels, intravenous, OGTT, serum insulin and C‑peptide were significantly recovered in the diabetic minipigs with the autologous BMSC (DMAB) transplantation group. In addition, the number of islets was significantly increased in this group compared to the diabetic minipig control (DMC) group with conventional therapy. These data suggested the implantation of autologous BMSCs for type 1 diabetes treatment can partially restore the function of islet β cells and maintain blood glucose homeostasis. Transplanted autologous BMSCs may improve islet repairing by differentiating for new islets and change pancreatic microcirculation and be identified in a real‑time manner using MRI in vivo.

View Figures

View References

1	Haller MJ, Viener HL, Wasserfall C, Brusko T, Atkinson MA and Schatz DA: Autologous umbilical cord blood infusion for type 1 diabetes. Exp Hematol. 36:710–715. 2008. View Article : Google Scholar : PubMed/NCBI
2	Limbert C, Päth G, Jakob F and Seufert J: Beta-cell replacement and regeneration: strategies of cell-based therapy for type 1 diabetes mellitus. Diabetes Res Clin Pract. 79:389–399. 2008. View Article : Google Scholar : PubMed/NCBI
3	Hussain MA and Theise ND: Stem-cell therapy for diabetes mellitus. Lancet. 364:203–205. 2004. View Article : Google Scholar
4	Jurewicz M, Yang S, Augello A, et al: Congenic mesenchymal stem cell therapy reverses hyperglycemia in experimental type 1 diabetes. Diabetes. 59:3139–3147. 2010. View Article : Google Scholar : PubMed/NCBI
5	Zhao Y, Jiang Z, Zhao T, et al: Reversal of type 1 diabetes via islet β cell regeneration following immune modulation by cord blood-derived multipotent stem cells. BMC Med. 10:32012.
6	Tang DQ, Cao LZ, Burkhardt BR, Xia CQ, Litherland SA, Atkinson MA and Yang LJ: In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes. 53:1721–1732. 2004. View Article : Google Scholar : PubMed/NCBI
7	Ianus A, Holz GG, Theise ND and Hussain MA: In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest. 111:843–850. 2003. View Article : Google Scholar : PubMed/NCBI
8	Lee RH, Seo MJ, Reger RL, Spees JL, Pulin AA, Olson SD and Prockop DJ: Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice. Proc Natl Acad Sci USA. 103:17438–17443. 2006. View Article : Google Scholar : PubMed/NCBI
9	Gao X, Song L, Shen K, Wang H, Niu W and Qin X: Transplantation of bone marrow derived cells promotes pancreatic islet repair in diabetic mice. Biochem Biophys Res Commun. 371:132–137. 2008. View Article : Google Scholar : PubMed/NCBI
10	Hasegawa Y, Ogihara T, Yamada T, et al: Bone marrow (BM) transplantation promotes beta-cell regeneration after acute injury through BM cell mobilization. Endocrinology. 148:2006–2015. 2007. View Article : Google Scholar : PubMed/NCBI
11	Urbán VS, Kiss J, Kovács J, Gócza E, Vas V, Monostori E and Uher F: Mesenchymal stem cells cooperate with bone marrow cells in therapy of diabetes. Stem Cells. 26:244–253. 2008.PubMed/NCBI
12	Couri CE and Voltarelli JC: Autologous stem cell transplantation for early type 1 diabetes mellitus. Autoimmunity. 41:666–672. 2008. View Article : Google Scholar : PubMed/NCBI
13	Larsen MO, Wilken M, Gotfredsen CF, Carr RD, Svendsen O and Rolin B: Mild streptozotocin diabetes in the Göttingen minipig. A novel model of moderate insulin deficiency and diabetes. Am J Physiol Endocrinol Metab. 282:E1342–E1351. 2002.
14	Larsen MO, Rolin B, Wilken M, Carr RD and Gotfredsen CF: Measurements of insulin secretory capacity and glucose tolerance to predict pancreatic beta-cell mass in vivo in the nicotinamide/streptozotocin Göttingen minipig, a model of moderate insulin deficiency and diabetes. Diabetes. 52:118–123. 2003.PubMed/NCBI
15	Hara H, Lin YJ, Zhu X, et al: Safe induction of diabetes by high-dose streptozotocin in pigs. Pancreas. 36:31–38. 2008. View Article : Google Scholar : PubMed/NCBI
16	Wen Y, Ouyang J, Yang R, Chen J, Liu Y, Zhou X and Burt RK: Reversal of new-onset type 1 diabetes in mice by syngeneic bone marrow transplantation. Biochem Biophys Res Commun. 374:282–287. 2008. View Article : Google Scholar : PubMed/NCBI
17	Ezquer FE, Ezquer ME, Parrau DB, Carpio D, Yañez AJ and Conget PA: Systemic administration of multipotent mesenchymal stromal cells reverts hyperglycemia and prevents nephropathy in type 1 diabetic mice. Biol Blood Marrow Transplant. 14:631–640. 2008. View Article : Google Scholar : PubMed/NCBI
18	Chang C, Niu D, Zhou H, Zhang Y, Li F and Gong F: Mesenchymal stroma cells improve hyperglycemia and insulin deficiency in the diabetic porcine pancreatic microenvironment. Cytotherapy. 10:796–805. 2008. View Article : Google Scholar : PubMed/NCBI
19	Olmos PR and Borzone G: Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 302:624author reply 624–625. 2009. View Article : Google Scholar
20	Couri CE, Oliveira MC, Stracieri AB, et al: C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 301:1573–1579. 2009. View Article : Google Scholar
21	Scolding N, Marks D and Rice C: Autologous mesenchymal bone marrow stem cells: practical considerations. J Neurol Sci. 265:111–115. 2008. View Article : Google Scholar : PubMed/NCBI
22	Yamout B, Hourani R, Salti H, et al: Bone marrow mesenchymal stem cell transplantation in patients with multiple sclerosis: a pilot study. J Neuroimmunol. 227:185–189. 2010. View Article : Google Scholar : PubMed/NCBI
23	Jirák D1, Kríz J, Herynek V, et al: MRI of transplanted pancreatic islets. Magn Reson Med. 52:1228–1233. 2004.
24	Neri M, Maderna C, Cavazzin C, et al: Efficient in vitro labeling of human neural precursor cells with superparamagnetic iron oxide particles: relevance for in vivo cell tracking. Stem Cells. 26:505–516. 2008. View Article : Google Scholar : PubMed/NCBI
25	Amsalem Y, Mardor Y, Feinberg MS, et al: Iron-oxide labeling and outcome of transplanted mesenchymal stem cells in the infarcted myocardium. Circulation. 116(Suppl 11): I38–I45. 2007. View Article : Google Scholar : PubMed/NCBI
26	Murray HE, Paget MB, Bailey CJ and Downing R: Sustained insulin secretory response in human islets co-cultured with pancreatic duct-derived epithelial cells within a rotational cell culture system. Diabetologia. 52:477–485. 2009. View Article : Google Scholar
27	Lipsett M, Aikin R, Castellarin M, Hanley S, Jamal AM, Laganiere S and Rosenberg L: Islet neogenesis: a potential therapeutic tool in type 1 diabetes. Int J Biochem Cell Biol. 38:498–503. 2006. View Article : Google Scholar : PubMed/NCBI
28	Jeong JO, Kim MO, Kim H, et al: Dual angiogenic and neurotrophic effects of bone marrow-derived endothelial progenitor cells on diabetic neuropathy. Circulation. 119:699–708. 2009. View Article : Google Scholar : PubMed/NCBI
29	Shibata T, Naruse K, Kamiya H, et al: Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic polyneuropathy in rats. Diabetes. 57:3099–3107. 2008. View Article : Google Scholar : PubMed/NCBI
30	Kin T, Korbutt GS, Kobayashi T, Dufour JM and Rajotte RV: Reversal of diabetes in pancreatectomized pigs after transplantation of neonatal porcine islets. Diabetes. 54:1032–1039. 2005. View Article : Google Scholar
31	Tang KX, Yan JH, Shen YF, et al: Tracing type 1 diabetic Tibet miniature pig’s bone marrow mesenchymal stem cells in vitro by magnetic resonance imaging. J Diabetes. 6:123–131. 2014.PubMed/NCBI
32	Layton DS, Strom AD, O’Neil TE, et al: Development of an anti-porcine CD34 monoclonal antibody that identifies hematopoietic stem cells. Exp Hematol. 35:171–178. 2007. View Article : Google Scholar : PubMed/NCBI
33	Nir T, Melton DA and Dor Y: Recovery from diabetes in mice by beta cell regeneration. J Clin Invest. 117:2553–2561. 2007. View Article : Google Scholar : PubMed/NCBI
34	Alvarez SS, Jimenez LM, Murillo AZ, et al: A new approach for bone marrow-derived stem cells intrapancreatic autotransplantation in diabetic rats. Microsurgery. 26:539–542. 2006. View Article : Google Scholar : PubMed/NCBI
35	Frank JA, Miller BR, Arbab AS, et al: Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology. 228:480–487. 2003. View Article : Google Scholar
36	Barnett BP, Arepally A, Karmarkar PV, et al: Magnetic resonance-guided, real-time targeted delivery and imaging of magnetocapsules immunoprotecting pancreatic islet cells. Nat Med. 13:986–991. 2007. View Article : Google Scholar