Therapeutic Potential of Adipose-Derived Stem Cells and Macrophages for Ischemic Skeletal Muscle Repair

Rybalko, Viktoriya; Hsieh, Pei‐Ling; Ricles, Laura M.; Chung, Eunna; Farrar, Roger P.; Suggs, Laura J.

doi:10.2217/rme-2016-0094

Cited by 27 publications

(28 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This has become even more relevant since recent studies showed that M1-polarized macrophages predominate in inflamed subcutaneous tissue of non-healing wounds [ 30 ]. On the contrary, ASC-cytokines induced an M2-like macrophage phenotype in vitro, and in vivo the beneficial effects of a combined macrophage/ASC treatment were demonstrated in a mouse model [ 31 ]. These findings would suggest a combined macrophages/ASC cell therapy also for non-healing wounds, such as ulcers and burn injuries.…”

Section: Discussionmentioning

confidence: 99%

Human Macrophages Preferentially Infiltrate the Superficial Adipose Tissue

Cappellano

Morandi

Rainer

et al. 2018

IJMS

View full text Add to dashboard Cite

Human abdominal subcutaneous adipose tissue consists of two individual layers—the superficial adipose tissue (SAT) and deep adipose tissue (DAT)—separated by the Scarpa’s fascia. The present study focuses on the analysis of morphological and immunological differences of primary adipocytes, adipose-derived stem cells (ASC), and tissue-infiltrating immune cells found in SAT and DAT. Adipocytes and stromal vascular fraction (SVF) cells were isolated from human SAT and DAT specimens and phenotypically characterized by in vitro assays. Ex vivo analysis of infiltrating immune cells was performed by flow cytometry. Primary adipocytes from SAT are larger in size but did not significantly differ in cytokine levels of LEPTIN, ADIPOQ, RBP4, CHEMERIN, DEFB1, VISFATIN, MCP1, or MSCF. ASC isolated from SAT proliferated faster and exhibited a higher differentiation potential than those isolated from DAT. Flow cytometry analysis indicated no specific differences in the relative numbers of ASC, epithelial progenitor cells (EPC), or CD3+ T-cells, but showed higher numbers of tissue-infiltrating macrophages in SAT compared to DAT. Our findings suggest that ASC isolated from SAT have a higher regenerative potential than DAT-ASC. Moreover, spatial proximity to skin microbiota might promote macrophage infiltration in SAT.

show abstract

Section: Discussionmentioning

confidence: 99%

Human Macrophages Preferentially Infiltrate the Superficial Adipose Tissue

Cappellano

Morandi

Rainer

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…Finally, they may affect the remodeling of the regenerating muscle and the maturation of muscle cells, perhaps by a direct effect of ASCs migrating to affected muscles as reported previously (Vieira et al, 2012). Thus, ASCs could directly act on muscle recovery and enhance muscle regeneration (Rodriguez et al, 2005;Rybalko et al, 2017). By immunostaining of human nuclear marker Ku80 (Koike et al, 1999;Allard et al, 2014), we addressed settlement of systemically applied ASCs in muscles (Supplementary Figure S5).…”

Section: Effects Of Ascs On De/regeneration Of Muscle and Nmjsmentioning

confidence: 91%

Effects of ASC Application on Endplate Regeneration Upon Glycerol-Induced Muscle Damage

Rigon

Hörner

Straka

et al. 2020

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Amongst other approaches, adipose-derived stromal cells (ASCs) have recently been tested with respect to their regenerative capacity for treatment of neuromuscular disorders. While beneficial effects of ASCs on muscle recovery were observed previously, their impact on regeneration of neuromuscular junctions (NMJs) is unclear. Here, we used a murine glycerol damage model to study disruption and regeneration of NMJs and to evaluate the effects of systemic application of ASCs on muscle and NMJ recovery. In mice that were not treated with ASCs, a differential response of NMJ preand post-synapses to glycerol-induced damage was observed. While post-synapses were still present in regions that were necrotic and lacking actin and dystrophin, presynapses disappeared soon in those affected areas. Partial regeneration of NMJs occurred within 11 days after damage. ASC treatment slightly enhanced NMJ recovery and reduced the loss of presynaptic sites, but also led to a late phase of muscle necrosis and fibrosis. In summary, the results suggest a differential sensitivity of NMJ pre-and post-synapses to glycerol-induced muscle damage and that the use of ASC for the treatment of neuromuscular disorders needs further careful evaluation.

show abstract

“…Generally, ADSCs are known to secrete multiple angiogenic growth factors, including vascular endothelial growth factor and platelet‐derived growth factor . Rybalko et al reported therapeutic potential of ADSCs in ischemic skeletal muscle models through growth factor secreted by cultured adipose tissue–derived stromal cells. Nakagami et al confirmed that ADSCs are directly involved in the development of vasculogenesis in the damaged site of ischemic limb.…”

Section: Discussionmentioning

confidence: 99%

Potential of autologous adipose‐derived stem cells to regenerate atrophied muscle in a rat model

Park

Kwon

2017

Wound Repair Regeneration

View full text Add to dashboard Cite

Muscle atrophy results in severe functional impairment and is a significant clinical problem. We examined and characterized the therapeutic effects of autologous adipose-derived stem cells (ADSCs) using an in vivo muscle atrophy rat model. To identify the effect of injected ADSCs into muscle, we developed the following two models of muscle atrophy in rats: induction of denervation by sciatic nerve defects; and nerve repair after severing the sciatic nerve. The inguinal fat pads were harvested from each rat and autologous ADSCs were cultured and ADSCs were injected in the right hind limbs as the experimental group, while normal saline was injected in the left hind limbs, which served as the control group. After 2 weeks, gross examination and histologic analyses were performed. Additionally, to investigate the survival of ADSCs in muscle tissues, we traced the injected ADSCs. The fate of injected ADSCs into muscle was investigated using a green fluorescent protein (GFP) tagging method with lentivirus transfection. The muscle weight and cross-sectional area of muscle were greater and proliferation of connective tissue was less prominent in the ADSC-injected group. Alpha-bungarotoxin binding in the neuromuscular junction was significantly increased, and neoangiogenesis was higher in the ADSCs-injected group. green fluorescent protein-labeled ADSCs survived in the gastrocnemius muscle after 2 weeks. These findings could give a support in finding the role of autologous ADSCs as new therapeutic modality for regeneration of atrophied muscle.

show abstract

Therapeutic Potential of Adipose-Derived Stem Cells and Macrophages for Ischemic Skeletal Muscle Repair

Cited by 27 publications

References 56 publications

Human Macrophages Preferentially Infiltrate the Superficial Adipose Tissue

Human Macrophages Preferentially Infiltrate the Superficial Adipose Tissue

Effects of ASC Application on Endplate Regeneration Upon Glycerol-Induced Muscle Damage

Potential of autologous adipose‐derived stem cells to regenerate atrophied muscle in a rat model

Contact Info

Product

Resources

About