Viral vector delivery of follistatin enhances recovery of reinnervated muscle

Isaacs, Jonathan; Feger, Mark A.; Mallu, Satya; Yager, Dorne R.; Shall, Mary S.; Patel, Gaurangkumar; Protzuk, Omar; Graham, Lindsay T.

doi:10.1002/mus.26653

Cited by 4 publications

(8 citation statements)

References 55 publications

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“…Likewise, our prior investigation demonstrated that recombinant FST DNA also enhances satellite cell counts after denervation and repair. 25 In the current investigation, there did seem to be a correlation with satellite cell counts and force generation. In groups in which the satellite cell counts were diminished, (3-month sham denervation) force output was reduced and conversely in groups with bolstered satellite cell counts (6-month denervation) force output was enhanced.…”

Section: Discussioncontrasting

confidence: 39%

“… 29 We previously demonstrated improved muscle mass, increased type IIB muscle fiber size, and increased satellite cell counts in an identical study with the administration of FST DNA via viral vectors. 25 In contrast to transgenetic manipulation, however, the therapeutic potential of direct FST protein administration has received scant attention. Injecting spinal muscular atrophy mice with recombinant FST increased muscle mass, coordination, and life span.…”

Section: Discussionmentioning

confidence: 99%

“…There were no detectable levels of FST protein in treated and untreated muscles in the 6-month groups. Unlike genetically based FST treatment, 25 focal FST protein delivery would only elevate local levels of FST during the course of administration and analysis was completed 2 weeks after the reservoir was depleted. Any FST being quantified would be endogenously produced, and the failure to demonstrate FST even in untreated groups implies that local production of FST is impaired after 6 months of repeated surgical manipulations, temporary denervation, catheter irritation, and/or sedentary behavior.…”

Section: Discussionmentioning

confidence: 99%

“…The goal of our study was to evaluate the effects of recombinant FST protein when delivered locally to reinnervated muscle following temporary denervation periods of 3 or 6 months. We utilized the same previously published methods with viral vectors that expressed FST DNA, 25 and the current investigation utilizes the same protocol to assess the effect of direct protein delivery. Eight groups of male Sprague-Dawley rats (72 rats total) were used in the study ( Fig.…”

Section: Methodsmentioning

confidence: 99%

“…We recently demonstrated enhanced muscle mass and bolstered satellite cell pools in a companion study utilizing viral vectors expressing FST DNA. 25 However, for the focal weakness that might be seen with denervation atrophy, targeted administration of FST protein would seem more practical and clinically translatable.…”

Section: Introductionmentioning

confidence: 99%

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Follistatin Protein Enhances Satellite Cell Counts in Reinnervated Muscle

Feger

Isaacs

Mallu

et al. 2022

J Brachial Plex Peripher Nerve Inj

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Background Muscle recovery following peripheral nerve repair is sup-optimal. Follistatin (FST), a potent muscle stimulant, enhances muscle size and satellite cell counts following reinnervation when administered as recombinant FST DNA via viral vectors. Local administration of recombinant FST protein, if effective, would be more clinically translatable but has yet to be investigated following muscle reinnervation. Objective The aim of this study is to assess the effect of direct delivery of recombinant FST protein on muscle recovery following muscle reinnervation. Materials and Methods In total, 72 Sprague-Dawley rats underwent temporary (3 or 6 months) denervation or sham denervation. After reinnervation, rats received FST protein (isoform FS-288) or sham treatment via a subcutaneous osmotic pump delivery system. Outcome measures included muscle force, muscle histomorphology, and FST protein quantification. Results Follistatin treatment resulted in smaller muscles after 3 months denervation (p = 0.019) and reduced force after 3 months sham denervation (p < 0.001). Conversely, after 6 months of denervation, FST treatment trended toward increased force output (p = 0.066). Follistatin increased satellite cell counts after denervation (p < 0.001) but reduced satellite cell counts after sham denervation (p = 0.037). Conclusion Follistatin had mixed effects on muscle weight and force. Direct FST protein delivery enhanced satellite cell counts following reinnervation. The positive effect on the satellite cell population is intriguing and warrants further investigation.

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Section: Discussioncontrasting

confidence: 39%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Follistatin Protein Enhances Satellite Cell Counts in Reinnervated Muscle

Feger

Isaacs

Mallu

et al. 2022

J Brachial Plex Peripher Nerve Inj

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Follistatin expression in the central nervous system of the adult rat

Ogawa

Mikawa

Yamashita

et al. 2020

Journal of Chemical Neuroanatomy

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Cross-talk between hepatokines as Liver indused-exercise factors and organokines

rad

2023

Preprint

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Exercise not only improves the capacity of the skeletal muscles that perform contractions, but also provides health benefits and prevents a number of chronic diseases caused by physiological and biological changes throughout the body. For decades, intensive research has been carried out into the “exercise factors” that mediate these positive effects. In particular, skeletal muscle tissue has been studied as a source of circulating exercise factors and several myokines have been identified. However, Exercise also affects other tissues. The liver plays an important role in the tissues that store and use energy as well as it is very active during exercise and ensures the maintenance of energy homeostasis. Recently, a novel group of Liver indused-exercise factors termed hepatokines has emerged. Hepatokines can act in an autocrine/paracrine manner on the liver and as endocrine factors on brain, endothelium, adipose tissue, pancreas, heart, intestine, and skeletal muscle. In most cases, an acute bout of exercise increases the systemic concentration of hepatokines (FGF21, ANGPTL4, Follistatin, Selenoprotein P, HSP72 ,IGFBP, fetuin-A, fetuin-B, Hepassocin, Activin E, Chemerin, Adropin) and this factors released from the liver and increased in the bloodstream during or in the recovery after an exercise bout. It should be noted that in addition to liver tissue, there are also other hepatokines secreted and released by other tissues such as brain, adipocytes, intestine, heart, osteoblasts and melanoma. In this narrative review, we evaluate this new group of exercise factors focusing on the regulation and potential function in exercise metabolism and adaptations .These hepatokines may convey some of the beneficial whole-body effects of exercise and cross-talk with organokines and could ameliorate metabolic diseases, such as obesity or type 2 diabetes.

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Viral vector delivery of follistatin enhances recovery of reinnervated muscle

Cited by 4 publications

References 55 publications

Follistatin Protein Enhances Satellite Cell Counts in Reinnervated Muscle

Follistatin Protein Enhances Satellite Cell Counts in Reinnervated Muscle

Follistatin expression in the central nervous system of the adult rat

Cross-talk between hepatokines as Liver indused-exercise factors and organokines

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