Subcutaneous transplantation of engineered islet/adipose-derived mesenchymal stem cell sheets in diabetic pigs with total pancreatectomy
| Autor: | Shinichiro Ono, Kyoichiro Maekawa, Kengo Kanetaka, Mampei Yamashita, Tamotsu Kuroki, Masaaki Hidaka, Toshiyuki Adachi, Naomi Matsumura, Susumu Eguchi, Tomohiko Adachi, Yusuke Sakai |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Medicine (General) endocrine system diseases medicine.medical_treatment Adipose tissue Stimulation MSC mesenchymal stem cell 0302 clinical medicine Islet transplantation TGF transforming growth factor XIAP X-linked inhibitor of apoptosis protein geography.geographical_feature_category DMEM Dulbecco's modified Eagle's medium Subcutaneous ELISA enzyme-linked immunosorbent assay Islet Venous thrombosis Original Article IBMIR instant blood-mediated inflammatory reaction medicine.medical_specialty endocrine system Biomedical Engineering PBS phosphate-buffered saline Type 1 diabetes mellitus CGM continuous glucose monitor MEM minimum essential medium Biomaterials 03 medical and health sciences R5-920 FBS fetal bovine serum T1DM Type 1 diabetes mellitus Internal medicine Adipose-derived mesenchymal stem cells medicine ADSC adipose-derived mesenchymal stem cell Type 1 diabetes geography Pig QH573-671 business.industry Insulin Mesenchymal stem cell HSP32 heat shock protein 32 medicine.disease Transplantation 030104 developmental biology Endocrinology H & E hematoxylin and eosin IVGTT intravenous glucose tolerance test UW University of Wisconsin HGF hepatocyte growth factor IEQ islet equivalent business SD standard deviation Cytology 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Regenerative Therapy, Vol 16, Iss, Pp 42-52 (2021) Regenerative Therapy |
| ISSN: | 2352-3204 |
| Popis: | Introduction Intraportal islet transplantation is a promising therapeutic approach for patients with type 1 diabetes mellitus (T1DM). However, despite being minimally invasive, the method has some limitations, such as short-term graft loss, portal venous thrombosis, and difficulty in collecting adequate amounts of islets. Subcutaneous islet transplantation on adipose-derived mesenchymal stem cell (ADSC) sheets has been suggested to overcome these limitations, and in this study, we have examined its feasibility in T1DM pigs. Methods Inguinal subcutaneous fat was harvested from young pigs and then isolated and cultured adequate ADSCs to prepare sheets. Islets were isolated from the pancreases of mature pigs and seeded on the ADSC sheets. T1DM pigs were generated by total pancreatectomy, and ADSC sheets with transplanted islets were administered subcutaneously to the waist (n = 2). The effects of the islets on the ADSC sheets and on blood glucose levels were evaluated. Insulin secretion was measured by insulin stimulation index. Results Islet viability was higher on ADSCs compared to islets alone (91.8 ± 4.3 vs. 81.7 ± 4.1%). The insulin stimulation index revealed higher glucose sensitivity of islets on ADSC sheets compared to islets alone (2.8 ± 2.0 vs. 0.8 ± 0.3). After transplantation, the blood glucose levels of two pigs were within the normal range, and sensitive insulin secretion was confirmed by intravenous glucose tolerance tests. After graftectomy, decreased insulin secretion and hyperglycemia were observed. Conclusions Subcutaneous islet transplantation using ADSC sheets can regulate the blood glucose levels of T1DM pigs. Highlights • The adipose-derived mesenchymal stem cell sheet is useful to protect the islets. • Subcutaneous islet transplantation on sheet normalized blood glucose in diabetic pig. • Subcutaneous islet transplantation on sheet can be a useful tool. |
| Databáze: | OpenAIRE |
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