Primary Progenitor Muscle Cells for Regenerative Medicine: Standardization of Therapeutic Protocols and Optimized In Vivo Murine Model For Volumetric Muscle Loss
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License: CC BY-SA 4.0
Serval ID
serval:BIB_1F0BEA8F6038
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Primary Progenitor Muscle Cells for Regenerative Medicine: Standardization of Therapeutic Protocols and Optimized In Vivo Murine Model For Volumetric Muscle Loss
Journal
American Journal of Biomedical Science & Research
ISSN
2642-1747
Publication state
Published
Issued date
19/03/2020
Volume
8
Number
2
Pages
143-153
Language
english
Abstract
Skeletal muscle tissue engineering constitutes an emerging therapeutic repair strategy aiming for structural and functional restoration following
traumatic injury, deep burns, congenital malformation or surgical tumor removal. As for similar musculoskeletal acute and degenerative affections,
allogenic progenitor cell therapy represents a promising clinical approach to synergistically supplement traditional surgical care. Preliminary studies
have established the adequation of primary human fetal muscle progenitors (hFMPs) for applications in regenerative medicine. Such therapeutic
cell sources combined with bioresorbable scaffolds optimally integrate in murine muscle injury models without causing immune rejection. The
present work aimed at functional recovery assessment following standardized application of hFMPs in an optimized murine skeletal muscle wound
model. Cryopreserved hFMPs were initiated and culture-expanded before seeding in equine collagen scaffolds. Gastrocnemius muscles of C57BL/6
mice were injured following a standardized protocol. Resulting volume defects were treated with collagen constructs yielding marked hFMPs (105
cells/construct), constructs alone or remained untreated, assorted to appropriate internal controls. Histological and biomechanical analysis of
muscle tissue and integrated therapeutic constructs were performed at the time of surgery and during the following 8 weeks. Both therapeutic
protocols and in vivo models were optimized and standardized, based on internal experience concerning progenitor cell therapies for cutaneous
reconstruction. Results indicated significantly improved function in all study groups treated with hFMPs. In particular, absolute peak twitch tensions
measured on injured muscles were relatively superior in value at different time points after progenitor cell therapy application. Engraftment of
hFMPs in murine wounded muscle enabled xenogeneic tissue repair stimulation and overall improvement of functional recovery. The combination
of murine muscle wound model and therapeutic cell delivery method was determined as optimal for assessing muscle functional characteristic
evolution notwithstanding severe tissue injury by volume loss. Such data support further translational investigation of allogenic progenitor cell
therapy for human muscle defects and injuries.
traumatic injury, deep burns, congenital malformation or surgical tumor removal. As for similar musculoskeletal acute and degenerative affections,
allogenic progenitor cell therapy represents a promising clinical approach to synergistically supplement traditional surgical care. Preliminary studies
have established the adequation of primary human fetal muscle progenitors (hFMPs) for applications in regenerative medicine. Such therapeutic
cell sources combined with bioresorbable scaffolds optimally integrate in murine muscle injury models without causing immune rejection. The
present work aimed at functional recovery assessment following standardized application of hFMPs in an optimized murine skeletal muscle wound
model. Cryopreserved hFMPs were initiated and culture-expanded before seeding in equine collagen scaffolds. Gastrocnemius muscles of C57BL/6
mice were injured following a standardized protocol. Resulting volume defects were treated with collagen constructs yielding marked hFMPs (105
cells/construct), constructs alone or remained untreated, assorted to appropriate internal controls. Histological and biomechanical analysis of
muscle tissue and integrated therapeutic constructs were performed at the time of surgery and during the following 8 weeks. Both therapeutic
protocols and in vivo models were optimized and standardized, based on internal experience concerning progenitor cell therapies for cutaneous
reconstruction. Results indicated significantly improved function in all study groups treated with hFMPs. In particular, absolute peak twitch tensions
measured on injured muscles were relatively superior in value at different time points after progenitor cell therapy application. Engraftment of
hFMPs in murine wounded muscle enabled xenogeneic tissue repair stimulation and overall improvement of functional recovery. The combination
of murine muscle wound model and therapeutic cell delivery method was determined as optimal for assessing muscle functional characteristic
evolution notwithstanding severe tissue injury by volume loss. Such data support further translational investigation of allogenic progenitor cell
therapy for human muscle defects and injuries.
Keywords
Cell therapy, Tissue engineering, Regenerative Medicine, Progenitor cells, Volumetric muscle loss, Biomechanical analysis, Murine model
Open Access
Yes
Create date
26/05/2020 6:45
Last modification date
25/06/2020 7:08