title: Hypoxic Preconditioning Improves the Therapeutic Potential of Aging Bone Marrow Mesenchymal Stem Cells in Streptozotocin-Induced Type-1 Diabetic Mice.
abstract: Insulin replacement is the current therapeutic option for type-1 diabetes. However, exogenous insulin cannot precisely represent the normal pattern of insulin secretion. Another therapeutic strategy is transplantation of pancreatic islets, but this is limited by immune rejection, intrinsic complications, and lack of donor availability. Stem cell therapy that results in the regeneration of insulin-producing cells represents an attractive choice. However, with advancing age, stem cells also undergo senescence, which leads to changes in the function of various cellular processes that result in a decrease in the regeneration potential of these aging stem cells. In this study, the effect of young and aging mesenchymal stem cells (MSCs) on the regeneration of pancreatic beta cells in streptozotocin (STZ)-induced type-1 diabetic mice was observed after hypoxic preconditioning. Hypoxia was chemically induced by 2, 4-dinitrophenol (DNP). Plasma insulin and glucose levels were measured at various time intervals, and pancreatic sections were analyzed histochemically. The effect of DNP was also analyzed on apoptosis of MSCs by flow cytometry and on gene expression of certain growth factors by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). We observed that hypoxic preconditioning caused changes in the gene expression levels of growth factors in both young and aging MSCs. Young MSCs showed significant regeneration potential compared with the aging cells in vivo. However, hypoxic preconditioning was able to improve the regeneration potential of aging MSCs. It is concluded from the present study that the regeneration potential of aging MSCs into pancreatic β-cells can be enhanced by hypoxic preconditioning, which causes changes in the gene expression of certain growth factors.
authors: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi , Karachi, Pakistan .
authors: Muhammad
authors: M
authors: Waseem
authors: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi , Karachi, Pakistan .
authors: Irfan
authors: I
authors: Khan
authors: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi , Karachi, Pakistan .
authors: Hana'a
authors: H
authors: Iqbal
authors: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi , Karachi, Pakistan .
authors: Sana
authors: S
authors: Eijaz
authors: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi , Karachi, Pakistan .
authors: Shumaila
authors: S
authors: Usman
authors: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi , Karachi, Pakistan .
authors: Nazia
authors: N
authors: Ahmed
authors: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi , Karachi, Pakistan .
authors: Gulzar
authors: G
authors: Alam
authors: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi , Karachi, Pakistan .
authors: Asmat
authors: A
authors: Salim
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D016922:Cellular Senescence; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000628:therapy*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000628:therapy*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D000860:Hypoxia; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D012038:Regeneration
chemical_list: D036341:Intercellular Signaling Peptides and Proteins