TY - JOUR
T1 - Optimizing mesenchymal stem cell extracellular vesicles for chronic wound healing
T2 - Bioengineering, standardization, and safety
AU - Shimizu, Yusuke
AU - Ntege, Edward Hosea
AU - Inoue, Yoshikazu
AU - Matsuura, Naoki
AU - Sunami, Hiroshi
AU - Sowa, Yoshihiro
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/6
Y1 - 2024/6
N2 - Chronic wounds represent a significant global burden, afflicting millions with debilitating complications. Despite standard care, impaired healing persists due to factors like persistent inflammation and impaired tissue regeneration. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) offer an innovative regenerative medicine approach, delivering stem cell-derived therapeutic cargo in engineered nanoscale delivery systems. This review examines pioneering bioengineering strategies to engineer MSC-EVs into precision nanotherapeutics for chronic wounds. Emerging technologies like CRISPR gene editing, microfluidic manufacturing, and biomimetic delivery systems are highlighted for their potential to enhance MSC-EV targeting, optimize therapeutic cargo enrichment, and ensure consistent clinical-grade production. However, key hurdles remain, including batch variability, rigorous safety assessment for potential tumorigenicity, immunogenicity, and biodistribution profiling. Crucially, collaborative frameworks harmonizing regulatory science with bioengineering and patient advocacy hold the key to expediting global clinical translation. By overcoming these challenges, engineered MSC-EVs could catalyze a new era of off-the-shelf regenerative therapies, restoring hope and healing for millions afflicted by non-healing wounds.
AB - Chronic wounds represent a significant global burden, afflicting millions with debilitating complications. Despite standard care, impaired healing persists due to factors like persistent inflammation and impaired tissue regeneration. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) offer an innovative regenerative medicine approach, delivering stem cell-derived therapeutic cargo in engineered nanoscale delivery systems. This review examines pioneering bioengineering strategies to engineer MSC-EVs into precision nanotherapeutics for chronic wounds. Emerging technologies like CRISPR gene editing, microfluidic manufacturing, and biomimetic delivery systems are highlighted for their potential to enhance MSC-EV targeting, optimize therapeutic cargo enrichment, and ensure consistent clinical-grade production. However, key hurdles remain, including batch variability, rigorous safety assessment for potential tumorigenicity, immunogenicity, and biodistribution profiling. Crucially, collaborative frameworks harmonizing regulatory science with bioengineering and patient advocacy hold the key to expediting global clinical translation. By overcoming these challenges, engineered MSC-EVs could catalyze a new era of off-the-shelf regenerative therapies, restoring hope and healing for millions afflicted by non-healing wounds.
KW - Bioengineering
KW - CRISPR
KW - Chronic wounds
KW - Extracellular vesicles
KW - Mesenchymal stem cells
KW - Regenerative medicine
UR - http://www.scopus.com/inward/record.url?scp=85195875982&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85195875982&partnerID=8YFLogxK
U2 - 10.1016/j.reth.2024.06.001
DO - 10.1016/j.reth.2024.06.001
M3 - Review article
AN - SCOPUS:85195875982
SN - 2352-3204
VL - 26
SP - 260
EP - 274
JO - Regenerative Therapy
JF - Regenerative Therapy
ER -