Muscle stem cell aging: regulation and rejuvenation

Sousa‐Victor, Pedro; García‐Prat, Laura; Serrano, Antonio L.; Perdiguero, Eusebio; Muñoz‐Cánoves, Pura

doi:10.1016/j.tem.2015.03.006

Cited by 135 publications

(119 citation statements)

References 108 publications

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“…Our most significant finding is the noxious impact of long-term T2D on the transcriptional signature of the MDSC and their ability to repair the corporal tissue, evidenced in the LD-SC exposed for 4–5 months to moderate hyperglycemia and severe dyslipidemia, As to the biological implications, there is increasing interest on the impact of normal aging in inducing senescence on stem cells (42), but it is less clear in the case of diabetes where causes may be more multifactorial and the damage may be more complex than that operating in aging (43). This MDSC impairment may resemble the one caused in differentiated cells that is intended to be counteracted by the injected stem cells.…”

Section: Discussionmentioning

confidence: 99%

Implanted Muscle-Derived Stem Cells Ameliorate Erectile Dysfunction in a Rat Model of Type 2 Diabetes, but Their Repair Capacity Is Impaired by Their Prior Exposure to the Diabetic Milieu

Kovanecz

Vernet

Masouminia

et al. 2016

The Journal of Sexual Medicine

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Introduction Muscle derived stem cells (MDSC) and other stem cells implanted into the penile corpora cavernosa ameliorate erectile dysfunction in type 1 diabetic (T1D) rat models by replenishing the lost corporal smooth muscle cells (SMC) and reducing fibrosis. However, no conclusive data on this question in T2/D/obesity models is available. Aim. We studied whether: a) MDSC from T2D Obese Zucker (OZ) rats at an early stage of diabetes (ED-SC), counteract corporal veno-occlusive dysfunction (CVOD) and corporal SMC loss/lipofibrosis when implanted in the OZ rats at a late stage of diabetes; b) MDSC from these late diabetes OZ rats (LD-SC) differ from ED-SC in their gene transcriptional phenotype and repair capacity. Methods and Outcomes ED-SC and LD-SC were compared by DNA microarray assays, and ED-SC were incubated in vitro under high glucose conditions (ED-HG-SC). These three MDSC types were injected into the corpora cavernosa of late diabetes OZ rats (OZ/ED, OZ/LD, and OZ/ED-HG rats respectively). Untreated OZ (OZ/UT) and non-diabetic Lean Zucker (LZ/UT) rats were controls. Two months later, rats were subjected to cavernosometry and the penile shaft and corporal tissues were subjected to histopathology and DNA microarray assays. Results Implanted ED-SC and ED-HG-SC, improved CVOD, counteracted corporal SMC/collagen decrease and fat infiltration in long-term T2D rats, and upregulated nNOS and eNOS. LD-SC acquired an inflammatory/profibrotic/oxidative/dyslipidemic transcriptional phenotype, and failed to repair the corporal tissue. Conclusions MDSC from pre-diabetic rats injected into the corpora cavernosa of long-term diabetic T2D rats improve CVOD and the underlying histopathology. In contrast, MDSC from long-term uncontrolled diabetic T2D rats, are imprinted by the hyperglycemic/dyslipidemic milieu with a noxious phenotype associated with an impaired tissue repair capacity. Diabetes-impacted stem cells may lack tissue repair efficacy as autografts, and should either be reprogrammed in vitro, or substituted by stem cells from allogenic non-diabetic sources.

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Section: Discussionmentioning

confidence: 99%

Implanted Muscle-Derived Stem Cells Ameliorate Erectile Dysfunction in a Rat Model of Type 2 Diabetes, but Their Repair Capacity Is Impaired by Their Prior Exposure to the Diabetic Milieu

Kovanecz

Vernet

Masouminia

et al. 2016

The Journal of Sexual Medicine

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“…Upon activation, satellite cells give rise to committed myogenic progenitors, which engage the myogenic program to generate new myofibers to sustain regeneration and/or muscle growth. Several studies support the idea that aging affects both the myofiber and satellite cell function [15,16].…”

Section: Introductionmentioning

confidence: 78%

Sarcopenia: a histological and immunohistochemical study on age-related muscle impairment

et al. 2015

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“…Although there has been debate regarding the requirements for PAX7 in satellite cell maintenance and muscle repair 24 , recent efforts have affirmed an absolute requirement for PAX7 in satellite cell proliferation and self-renewal, and hence, for efficient repair of muscle after injury 25–27 . Functional loss of the satellite cell pool has been observed in association with age-related muscle dysfunction and other muscle degenerative pathologies 28, 29 , highlighting the critical need to maintain this unique cell population in order to sustain effective regenerative function over a lifetime.…”

Section: Introductionmentioning

confidence: 99%

Molecular circuitry of stem cell fate in skeletal muscle regeneration, ageing and disease

Almada

Wagers

2016

Nat Rev Mol Cell Biol

256

246

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Satellite cells are adult myogenic stem cells that function to repair damaged muscle. The enduring capacity for muscle regeneration requires efficient satellite cell expansion after injury, differentiation to produce myoblasts that can reconstitute damaged fibers, and self-renewal to replenish the muscle stem cell pool for subsequent rounds of injury and repair. Emerging studies indicate that misregulations of satellite cell fate and function contribute to age-associated muscle dysfunction and influence the severity of muscle diseases, including Duchenne Muscular Dystrophy (DMD). It has also become apparent that satellite cell fate during muscle regeneration, aging, and in the context of DMD is governed by an intricate network of intrinsic and extrinsic regulators. Targeted manipulation of this network may offer unique opportunities for muscle regenerative medicine.

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Muscle stem cell aging: regulation and rejuvenation

Cited by 135 publications

References 108 publications

Implanted Muscle-Derived Stem Cells Ameliorate Erectile Dysfunction in a Rat Model of Type 2 Diabetes, but Their Repair Capacity Is Impaired by Their Prior Exposure to the Diabetic Milieu

Implanted Muscle-Derived Stem Cells Ameliorate Erectile Dysfunction in a Rat Model of Type 2 Diabetes, but Their Repair Capacity Is Impaired by Their Prior Exposure to the Diabetic Milieu

Sarcopenia: a histological and immunohistochemical study on age-related muscle impairment

Molecular circuitry of stem cell fate in skeletal muscle regeneration, ageing and disease

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