Journal de recherche et de thérapie sur les cellules souches

Abstrait

Targeted Delivery of Adipose Derived Stem Cells into a Transplant by Direct Intra-Arterial Administration

Amir Inbal, Meirav Sela, Vyacheslav Kalchenko, Yuri Kuznetsov, Or Friedman, Arik Zaretski, Gal Tirza, Dov Zipori, Eyal Gur and Nir Shani

Objective: Mesenchymal Stem Cells (MSCs) are adult multipotent cells that possess regenerative and immunosuppressant properties. Homing of MSCs to target organs remains a major challenge as intravenous delivery results in intravascular entrapment of most MSCs in vascularized organs. Intra-Arterial (IA) administration of MSCs to arteries feeding a specific organ improved the delivery of cells to these organs but often resulted in vessels obstruction. To improve targeting of MSCs into a transplant we designed a novel method for IA delivery of MSCs during the transplantation procedure. This study was aimed at evaluating the safety and efficacy of this method.

Methods: A syngeneic groin free flap between Lewis rats was performed in all experiment groups. Treatment groups included 3 groups (n ≥ 7) in which 1 × 106, 0.5 × 106 or 0.05 × 106 adipose derived MSCs (ASCs) were administered via a femoral artery branch prior to the final reperfusion of the flap. In vivo real time fluorescence imaging and intravital microscopy were used to define ASCs IA movement after transplantation.

Results: High concentrations of ASCs per injection resulted in poor flap survival rates (14.3%) due to flap necrosis. At 0.05 × 106 ASCs, increased long-term flap viability rates (85%) were observed. Whole-body imaging of fluorescently labeled ASCs demonstrated significant targeting of cells into the flap even at such a low cell quantity. ASCs were detected in proximity to small blood vessels within the viable flap.

Conclusions: Local IA administration of ASCs into a vascularized transplant/flap is feasible and allows high local cell concentrations with minimal cell dosing.