Therapeutic Potential of Adipose-Derived Therapeutic Factor Concentrate for Treating Critical Limb Ischemia
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
26525042
DOI
10.3727/096368915x689767
PII: content-CT-1472_Prochazka_et_al
Knihovny.cz E-resources
- MeSH
- Cytokines therapeutic use MeSH
- Neovascularization, Physiologic drug effects MeSH
- Hepatocyte Growth Factor metabolism MeSH
- Injections, Intramuscular MeSH
- Ischemia drug therapy MeSH
- Rabbits MeSH
- Culture Media, Conditioned pharmacology MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Mesenchymal Stem Cells metabolism MeSH
- Intercellular Signaling Peptides and Proteins therapeutic use MeSH
- Flow Cytometry MeSH
- Adipose Tissue metabolism MeSH
- Vascular Endothelial Growth Factor A metabolism MeSH
- Hindlimb pathology MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Cytokines MeSH
- Hepatocyte Growth Factor MeSH
- Culture Media, Conditioned MeSH
- Intercellular Signaling Peptides and Proteins MeSH
- Vascular Endothelial Growth Factor A MeSH
Transplantation of adipose-derived stem cells (ADSCs) is an emerging therapeutic option for addressing intractable diseases such as critical limb ischemia (CLI). Evidence suggests that therapeutic effects of ADSCs are primarily mediated through paracrine mechanisms rather than transdifferentiation. These secreted factors can be captured in conditioned medium (CM) and concentrated to prepare a therapeutic factor concentrate (TFC) composed of a cocktail of beneficial growth factors and cytokines that individually and in combination demonstrate disease-modifying effects. The ability of a TFC to promote reperfusion in a rabbit model of CLI was evaluated. A total of 27 adult female rabbits underwent surgery to induce ischemia in the left hindlimb. An additional five rabbits served as sham controls. One week after surgery, the ischemic limbs received intramuscular injections of either (1) placebo (control medium), (2) a low dose of TFC, or (3) a high dose of TFC. Limb perfusion was serially assessed with a Doppler probe. Blood samples were analyzed for growth factors and cytokines. Tissue was harvested postmortem on day 35 and assessed for capillary density by immunohistochemistry. At 1 month after treatment, tissue perfusion in ischemic limbs treated with a high dose of TFC was almost double (p < 0.05) that of the placebo group [58.8 ± 23 relative perfusion units (RPU) vs. 30.7 ± 13.6 RPU; mean ± SD]. This effect was correlated with greater capillary density in the affected tissues and with transiently higher serum levels of the angiogenic and prosurvival factors vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). The conclusions from this study are that a single bolus administration of TFC demonstrated robust effects for promoting tissue reperfusion in a rabbit model of CLI and that a possible mechanism of revascularization was promotion of angiogenesis by TFC. Results of this study demonstrate that TFC represents a potent therapeutic cocktail for patients with CLI, many of whom are at risk for amputation of the affected limb.
References provided by Crossref.org
Current Status of Cell-Based Therapy in Patients with Critical Limb Ischemia