Mesenchymal Stem Cell Spheroids for Immune Rejection Suppression
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Solution Overview
Problem
Current immunosuppressive therapies for pancreatic islet cell transplantation, such as those using MMF, rapamycin, and other drugs, fail to achieve long-term survival and functional insulin secretion in humans due to limitations in suppressing immune rejection, particularly in primates and humans, despite promising results in rodents.
Innovation Solution
Development of spheroids composed of mesenchymal stem cells and rapamycin microparticles with increased PD-L1 expression, which are used to suppress immune rejection by encapsulating rapamycin in a polymer, mixing with stem cells, and forming cell-particle fusion spheroids to enhance immune tolerance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If conventional immunosuppressive agents (MMF, rapamycin, cyclosporine) are used to suppress T-cell responses, then short-term survival of transplanted pancreatic islet cells is improved, but long-term survival and functional insulin secretion are not achieved
Solution Approach 1:
The invention uses a composite structure consisting of mesenchymal stem cells loaded with rapamycin microparticles. This composite system combines the immunosuppressive effect of rapamycin with the protective and immunomodulatory properties of mesenchymal stem cells, creating a synergistic effect that achieves both short-term and long-term immunosuppression while maintaining insulin secretion function
Solution Approach 2:
Mesenchymal stem cells act as an intermediary carrier that delivers rapamycin to the transplanted pancreatic islet cells. The stem cells protect the islet cells from immune rejection while providing controlled release of rapamycin, thereby mediating between the immunosuppressive drug and the target cells to achieve sustained protection
2Quantity of substance
If porcine pancreatic islet cells are transplanted into humans (xenotransplantation), then the availability of transplant material is improved, but immune rejection by T cells and B cells occurs
Solution Approach 1:
The invention converts the harmful immune rejection response into a beneficial outcome by using the immune response itself to activate and deliver immunosuppressive therapy. The xenotransplantation triggers immune response, which in turn activates the mesenchymal stem cells to release rapamycin and express PD-L1, ultimately suppressing the rejection and achieving long-term acceptance of the porcine islet cells
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The spheroids with increased PD-L1 expression effectively suppress T-cell responses and inflammatory reactions, leading to prolonged survival and maintained insulin secretion of transplanted pancreatic islet cells, serving as a therapeutic agent for diabetes treatment.
Implementation Method 1
spheroids with increased PD-L1 expression, including mesenchymal stem cells and rapamycin microparticles
Data Source
AI summary
The present disclosure relates to spheroids for suppressing immune rejection including mesenchymal stem cells and rapamycin microparticles, uses thereof, and a preparation method thereof, wherein the spheroids includes the mesenchymal stem cells and rapamycin microparticles have increased PD-L1 expression of mesenchymal stem cells by the rapamycin microparticles such that the spheroids in which PD-L1 expression on the surface is increased suppress T cells and inflammatory responses that induce immune rejection to the pancreatic islet cells transplanted in vivo, thereby exhibiting the effect of maintaining a survival period and insulin secretion functions of transplanted pancreatic islet cells for a long time.