From Mesenchymal Stromal/Stem Cells to Insulin-Producing Cells: Progress and Challenges

Area of Science:

• Cell therapy
• Diabetes mellitus research
• Immunomodulation

Background:

• Mesenchymal stromal cells (MSCs) are explored for type 1 diabetes mellitus (DM) cell therapy.
• MSCs offer advantages like non-teratogenicity, non-immunogenicity, and immunomodulatory functions.
• Sources include bone marrow and adipose tissue, with bone marrow MSCs being extensively studied.

Purpose of the Study:

• To investigate the potential of MSCs for generating insulin-producing cells (IPCs) for type 1 DM therapy.
• To explore the immunomodulatory mechanisms of MSCs and their potential role in maintaining IPC function post-transplantation.
• To identify key considerations for clinical translation, including transplantation sites and scaffold requirements.

Main Methods:

• Directed differentiation of MSCs into IPCs using glucose-rich media and growth factors.
• Assessment of IPC function in controlling chemically-induced diabetes in immune-deficient mice.
• Analysis of MSC immunomodulatory mechanisms, including PD-L1/PD-L2 expression and interaction with T lymphocytes.

Main Results:

• Differentiated MSCs (IPCs) demonstrated the ability to control chemically-induced diabetes in mice, comparable to pluripotent cell derivatives.
• MSC immunomodulation involves cell-to-cell contact and soluble factors, leading to increased T-regulatory cells.
• PD-L1 and PD-L2 expression on MSCs under inflammation suggests a mechanism for immune evasion.

Conclusions:

• MSCs are a viable source for generating IPCs for type 1 DM therapy.
• Understanding MSC immunomodulation is crucial for long-term graft survival and avoiding immunosuppression.
• Further research is required to address pre-clinical challenges, such as antibody effects and functional longevity, before clinical translation.