Combination of MSC spheroids wrapped within autologous composite sheet dually protects against immune rejection and enhances stem cell transplantation efficacy.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Mesenchymal stem cells (MSCs) are widely used in transplantation therapy due to their multilineage differentiation potential, abundance, and immuno-modulating ability. However, the risk of allograft rejection limits their application. Here, we proposed a novel method to facilitate MSC transplantation with enhanced applicability and efficacy. We cultured human adipose-derived MSCs in a 3D culture under in vitro expansion conditions and under conventional 2D adherent culture conditions. MSC spheroids promoted extracellular matrix molecules that stimulate MSC proliferation, and produced more angiogenic cytokines such as vascular endothelial growth factor, hepatocyte growth factor, and fibroblast growth factor than 2D-cultured MSCs. Further, MSC spheroids showed increased IDO expression, increased proportion of M2 macrophages, and decreased macrophage proliferation, compared to 2D-cultured MSCs. Next, we proposed the wrapping of autologous cell sheets from the recipient around in-vitro-grown MSC spheroids to prevent allogenic immune rejection during transplantation. Myoblasts from C57BL/6 mice were used to prepare a stem cell composite sheet containing human-derived MSC spheres. The transplantation of MSC spheroids increased the survival rate and decreased the inflammatory response of the immunocompetent C57BL/6 ischemic mice. Thus, combining 3D-cultured MSC spheroid technology wit

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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