Modulating SPARC expression in mesenchymal stem cells improves MSCs-mediated skin regeneration and wound repair
- 1INEU-CONICET, FLENI
- 2Cátedra de Citología, Histología y Embriología, FCM, UNLP
Abstract
Mesenchymal stem cells (MSCs) have garnered significant attention over the past three decades due to their robust regenerative potential, primarily mediated through their paracrine activity, involving the release of soluble bioactive factors and extracellular vesicles (EVs). The MSC secretome plays a pivotal role in wound healing by influencing cellular migration, inflammation, angiogenesis, extracellular matrix (ECM) remodeling, and re-epithelialization. SPARC (Secreted Protein Acidic and Rich in Cysteine), a multifunctional ECM glycoprotein involved in tissue repair and remodeling, regulates key processes such as cell migration, proliferation, angiogenesis, and survival. Despite its known role in ECM dynamics, the impact of SPARC expression on the regenerative properties of MSCs remains underexplored. In this study, we hypothesized that SPARC overexpression in MSCs enhances their regenerative capacity. Using lentiviral systems, we generated SPARC-overexpressing (+ SPARC) and SPARC-knockdown (KD-SPARC) MSCs to investigate SPARC’s role in wound healing. Conditioned media (CM) derived from these MSCs were analyzed in vitro for their effects on human skin keratinocytes and fibroblasts. Our results revealed that SPARC expression significantly influences cell-specific migration and cell cycle progression. Furthermore, in an in vivo wound healing model, CM from +SPARC MSCs accelerated regeneration, whereas the absence of SPARC in MSC-derived CM delayed the healing process. These findings underscore the critical role of SPARC in modulating MSCs functionality and enhancing the regenerative efficacy of their CM. This study highlights SPARC as a promising therapeutic target for the development of advanced regenerative therapies aimed at improving cutaneous wound healing outcomes.
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BibTeX
@article{lombardi2026modulating,
title = {{Modulating SPARC expression in mesenchymal stem cells improves MSCs-mediated skin regeneration and wound repair}},
author = {A. Lombardi and J. Smucler and M. B. Palma and A. Iribarne and A. La Greca and M. N. García and A. Waisman and L. N. Moro and G. E. Sevlever and S. G. Miriuka and C. D. Luzzani},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-62848-x},
url = {https://doi.org/10.1038/s41598-026-62848-x},
note = {CC BY},
}
RIS
TY - JOUR
TI - Modulating SPARC expression in mesenchymal stem cells improves MSCs-mediated skin regeneration and wound repair
AU - A. Lombardi
AU - J. Smucler
AU - M. B. Palma
AU - A. Iribarne
AU - A. La Greca
AU - M. N. García
AU - A. Waisman
AU - L. N. Moro
AU - G. E. Sevlever
AU - S. G. Miriuka
AU - C. D. Luzzani
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-62848-x
UR - https://doi.org/10.1038/s41598-026-62848-x
AB - Mesenchymal stem cells (MSCs) have garnered significant attention over the past three decades due to their robust regenerative potential, primarily mediated through their paracrine activity, involving the release of soluble bioactive factors and extracellular vesicles (EVs). The MSC secretome plays a pivotal role in wound healing by influencing cellular migration, inflammation, angiogenesis, extracellular matrix (ECM) remodeling, and re-epithelialization. SPARC (Secreted Protein Acidic and Rich in Cysteine), a multifunctional ECM glycoprotein involved in tissue repair and remodeling, regulates key processes such as cell migration, proliferation, angiogenesis, and survival. Despite its known role in ECM dynamics, the impact of SPARC expression on the regenerative properties of MSCs remains underexplored. In this study, we hypothesized that SPARC overexpression in MSCs enhances their regenerative capacity. Using lentiviral systems, we generated SPARC-overexpressing (+ SPARC) and SPARC-knockdown (KD-SPARC) MSCs to investigate SPARC’s role in wound healing. Conditioned media (CM) derived from these MSCs were analyzed in vitro for their effects on human skin keratinocytes and fibroblasts. Our results revealed that SPARC expression significantly influences cell-specific migration and cell cycle progression. Furthermore, in an in vivo wound healing model, CM from +SPARC MSCs accelerated regeneration, whereas the absence of SPARC in MSC-derived CM delayed the healing process. These findings underscore the critical role of SPARC in modulating MSCs functionality and enhancing the regenerative efficacy of their CM. This study highlights SPARC as a promising therapeutic target for the development of advanced regenerative therapies aimed at improving cutaneous wound healing outcomes.
SN - 2045-2322
ER -