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Sci Rep. 2017 Aug 16;7(1):8484. doi: 10.1038/s41598-017-08921-y.

Umbilical cord extracts improve diabetic abnormalities in bone marrow-derived mesenchymal stem cells and increase their therapeutic effects on diabetic nephropathy.

Author information

1
Second Department of Anatomy, Sapporo Medical University, Sapporo, Japan. kanna@sapmed.ac.jp.
2
Department of Diabetic Cellular Therapeutics, Sapporo Medical University, Sapporo, Japan. kanna@sapmed.ac.jp.
3
Second Department of Anatomy, Sapporo Medical University, Sapporo, Japan.
4
Department of Diabetic Cellular Therapeutics, Sapporo Medical University, Sapporo, Japan.
5
Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, Japan.
6
Department of Gynecology and Obstetrics, NTT Sapporo Hospital, Sapporo, Japan.

Abstract

Bone marrow-derived mesenchymal stem cells (BM-MSC) has been applied as the most valuable source of autologous cell transplantation for various diseases including diabetic complications. However, hyperglycemia may cause abnormalities in intrinsic BM-MSC which might lose sufficient therapeutic effects in diabetic patients. We demonstrated the functional abnormalities in BM-MSC derived from both type 1 and type 2 diabetes models in vitro, which resulted in loss of therapeutic effects in vivo in diabetic nephropathy (DN). Then, we developed a novel method to improve abnormalities in BM-MSC using human umbilical cord extracts, namely Wharton's jelly extract supernatant (WJs). WJs is a cocktail of growth factors, extracellular matrixes and exosomes, which ameliorates proliferative capacity, motility, mitochondrial degeneration, endoplasmic reticular functions and exosome secretions in both type 1 and type 2 diabetes-derived BM-MSC (DM-MSC). Exosomes contained in WJs were a key factor for this activation, which exerted similar effects to complete WJs. DM-MSC activated by WJs ameliorated renal injury in both type 1 and type 2 DN. In this study, we developed a novel activating method using WJs to significantly increase the therapeutic effect of BM-MSC, which may allow effective autologous cell transplantation.

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