Therapeutic potential of adipose-derived therapeutic factor concentrate for treating critical limb Ischemia

Václav Procházka, Jana Jurčíková, Ondrej Laššák, Kateřina Vítková, Lubomír Pavliska, Ludmila Porubová, Piotr P. Buszman, Agata Krauze, Carlos Fernandez, František Jalůvka, Iveta Špačková, Ivo Lochman, Dvořáčková Jana, Stephanie Merfeld-Clauss, Keith L. March, Dmitry Traktuev, Brian H. Johnstone

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1623-1633
Number of pages11
JournalCell Transplantation
Volume25
Issue number9
DOIs
StatePublished - 2016

Fingerprint

Ischemia
Extremities
Tissue
Stem cells
Surgery
Perfusion
Therapeutics
Rabbits
Angiogenesis Inducing Agents
Blood
Reperfusion
Intercellular Signaling Peptides and Proteins
Stem Cells
Placebos
Cytokines
Hepatocyte Growth Factor
Intramuscular Injections
Therapeutic Uses
Hindlimb
Conditioned Culture Medium

Keywords

  • Critical limb ischemia (CLI)
  • Mesenchymal stem cells (MSCs)
  • Rabbit
  • Stromal vascular fraction
  • Therapeutic factor concentrate (TFC)

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

Cite this

Procházka, V., Jurčíková, J., Laššák, O., Vítková, K., Pavliska, L., Porubová, L., ... Johnstone, B. H. (2016). Therapeutic potential of adipose-derived therapeutic factor concentrate for treating critical limb Ischemia. Cell Transplantation, 25(9), 1623-1633. https://doi.org/10.3727/096368915X689767

Therapeutic potential of adipose-derived therapeutic factor concentrate for treating critical limb Ischemia. / Procházka, Václav; Jurčíková, Jana; Laššák, Ondrej; Vítková, Kateřina; Pavliska, Lubomír; Porubová, Ludmila; Buszman, Piotr P.; Krauze, Agata; Fernandez, Carlos; Jalůvka, František; Špačková, Iveta; Lochman, Ivo; Jana, Dvořáčková; Merfeld-Clauss, Stephanie; March, Keith L.; Traktuev, Dmitry; Johnstone, Brian H.

In: Cell Transplantation, Vol. 25, No. 9, 2016, p. 1623-1633.

Research output: Contribution to journalArticle

Procházka, V, Jurčíková, J, Laššák, O, Vítková, K, Pavliska, L, Porubová, L, Buszman, PP, Krauze, A, Fernandez, C, Jalůvka, F, Špačková, I, Lochman, I, Jana, D, Merfeld-Clauss, S, March, KL, Traktuev, D & Johnstone, BH 2016, 'Therapeutic potential of adipose-derived therapeutic factor concentrate for treating critical limb Ischemia', Cell Transplantation, vol. 25, no. 9, pp. 1623-1633. https://doi.org/10.3727/096368915X689767
Procházka V, Jurčíková J, Laššák O, Vítková K, Pavliska L, Porubová L et al. Therapeutic potential of adipose-derived therapeutic factor concentrate for treating critical limb Ischemia. Cell Transplantation. 2016;25(9):1623-1633. https://doi.org/10.3727/096368915X689767
Procházka, Václav ; Jurčíková, Jana ; Laššák, Ondrej ; Vítková, Kateřina ; Pavliska, Lubomír ; Porubová, Ludmila ; Buszman, Piotr P. ; Krauze, Agata ; Fernandez, Carlos ; Jalůvka, František ; Špačková, Iveta ; Lochman, Ivo ; Jana, Dvořáčková ; Merfeld-Clauss, Stephanie ; March, Keith L. ; Traktuev, Dmitry ; Johnstone, Brian H. / Therapeutic potential of adipose-derived therapeutic factor concentrate for treating critical limb Ischemia. In: Cell Transplantation. 2016 ; Vol. 25, No. 9. pp. 1623-1633.
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AU - Fernandez, Carlos

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AU - Lochman, Ivo

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