Enhancing in vivo survival of adipose-derived stromal cells through Bcl-2 overexpression using a minicircle vector.
Tissue regeneration using progenitor cell-based therapy has the potential to aid in the healing of a diverse range of pathologies, ranging from short-gut syndrome to spinal cord lesions. However, there are numerous hurdles to be overcome prior to the widespread application of these cells in the clinical setting. One of the primary barriers to effective stem cell therapy is the hostile environment that progenitor cells encounter in the clinical injury wound setting. In order to promote cellular survival, stem cell differentiation, and participation in tissue regeneration, relevant cells and delivery scaffolds must be paired with strategies to prevent cell death to ensure that these cells can survive to form de novo tissue. The Bcl-2 protein is a prosurvival member of a family of proteins that regulate the mitochondrial pathway of apoptosis. Using several strategies to overexpress the Bcl-2 protein, we demonstrated a decrease in the mediators of apoptosis in vitro and in vivo. This was shown through the use of two different clinical tissue repair models. Cells overexpressing Bcl-2 not only survived within the wound environment at a statistically significantly higher rate than control cells, but also increased tissue regeneration. Finally, we used a nonintegrating minicircle technology to achieve this in a potentially clinically applicable strategy for stem cell therapy.
Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Jeong
J
Hyun
Monica
M
Grova
Hossein
H
Nejadnik
David
D
Lo
Shane
S
Morrison
Daniel
D
Montoro
Michael
M
Chung
Andrew
A
Zimmermann
Graham G
GG
Walmsley
Min
M
Lee
Heike
H
Daldrup-Link
Derrick C
DC
Wan
Michael T
MT
Longaker
D000256:Adenoviridae / Q000235:genetics; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000287:Administration, Topical; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D008875:Middle Aged; D012038:Regeneration; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism / Q000821:virology; D014945:Wound Healing; D014949:Wounds, Nonpenetrating / Q000628:therapy*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D051028:bcl-2-Associated X Protein
Adult stem cells; Apoptosis; Cellular therapy; Gene delivery systems in vivo or in vitro