Adipose-Derived Stem Cells in a Resilient In Situ Forming Hydrogel Modulate Macrophage Phenotype.

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)

Injectable hydrogels have the potential to enhance stem cell-based therapies by improving cell localization, retention, and survival after transplantation. The inflammatory response to both the hydrogel and the encapsulated cells is a critical aspect of this strategy, with macrophages being highly involved in the process of hydrogel remodeling, angiogenesis, and tissue regeneration. As a step toward the development of a cell-based strategy for therapeutic angiogenesis, this work compared the intramuscular injection of allogeneic rat adipose-derived stem/stromal cells (rASCs) in an in situ gelling hydrogel with the injection of the hydrogel alone and rASCs in saline in an immunocompetent rat model by immunohistochemical analysis over 4 weeks. rASCs delivered in the hydrogel were retained intramuscularly at significantly higher densities as compared with cells delivered in saline. The encapsulated rASCs modulated the inflammatory response, promoting CD68 + macrophage recruitment, with the majority of infiltrating cells expressing the M1 marker CCR7, as well as a higher fraction of CD163 + M2c macrophages surrounding the hydrogel. Furthermore, rASCs reduced the initial expression of inducible nitric oxide synthase and promoted arginase-1 expression in the infiltrating macrophages over time, consistent with a shift toward a more proregenerative phenotype. Coincident with the enhanc

Evidence level

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

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