Journal article

Publication year: 2021

Journal: Stem Cell Research and Therapy

Volume number: 12

Issue number: 1

eISSN: 1757-6512

Open access status: Gold

DOI Link: https://doi.org/10.1186/s13287-021-02173-4

Publisher: BioMed Central

Abstract: 
BackgroundType 1 diabetes mellitus (T1D) is characterized by the autoimmune destruction of the pancreatic beta cells. The transplantation of mesenchymal stromal/stem cells (MSC) was reported to rescue the damaged pancreatic niche. However, there is an ongoing discussion on whether direct physical contact between MSC and pancreatic islets results in a superior outcome as opposed to indirect effects of soluble factors released from the MSC entrapped in the lung microvasculature after systemic administration. Hence, MSC were studied in direct contact (DC) and indirect contact (IDC) with murine pancreatic beta cell line MIN6-cells damaged by nitrosourea derivative streptozotocin (STZ) in vitro. Further, the protective and antidiabetic outcome of MSC transplantation was evaluated through the intrapancreatic route (IPR) and intravenous route (IVR) in STZ-induced diabetic NMRI nude mice.MethodsMSC were investigated in culture with STZ-damaged MIN6-cells, either under direct contact (DC) or separated through a semi-permeable membrane (IDC). Moreover, multiple low doses of STZ were administered to NMRI nude mice for the induction of hyperglycemia. 0.5x10(6) adipose-derived mesenchymal stem cells (ADMSC) were transferred through direct injection into the pancreas (IPR) or the tail vein (IVR), respectively. Bromodeoxyuridine (BrdU) was injected for the detection of proliferating islet cells in vivo, and real-time polymerase chain reaction (RT-PCR) was employed for the measurement of the expression of growth factor and immunomodulatory genes in the murine pancreas and human MSC. Phosphorylation of AKT and ERK was analyzed with Western blotting.ResultsThe administration of MSC through IPR ameliorated hyperglycemia in contrast to IVR, STZ, and non-diabetic control in a 30-day window. IPR resulted in a higher number of replicating islet cells, number of islets, islet area, growth factor (EGF), and balancing of the Th1/Th2 response in vivo. Physical contact also provided a superior protection to MIN6-cells from STZ through the AKT and ERK pathway in vitro in comparison with IDC.ConclusionOur study suggests that the physical contact between MSC and pancreatic islet cells is required to fully unfold their protective potential.

Harvard Citation style: Khatri, R., Petry, S. and Linn, T. (2021) Intrapancreatic MSC transplantation facilitates pancreatic islet regeneration, Stem Cell Research and Therapy, 12(1), Article 121. https://doi.org/10.1186/s13287-021-02173-4

APA Citation style: Khatri, R., Petry, S., & Linn, T. (2021). Intrapancreatic MSC transplantation facilitates pancreatic islet regeneration. Stem Cell Research and Therapy. 12(1), Article 121. https://doi.org/10.1186/s13287-021-02173-4