Tissue Eng Part A. 2012 May 4. [Epub ahead of print]
Transplantation of cord blood mesenchymal stem cells as spheroids enhances vascularization

Bhang SH, Lee S, Shin JY, Lee TJ, Kim BS.
Abstract

Despite promising results from the therapeutic use of stem cells for treating ischemic diseases, poor survival of cells transplanted into ischemic regions is one of the major problems that undermine the efficacy of stem cell therapy. Cord blood mononuclear cells (CBMNCs) are an alternative source of mesenchymal stem cells (MSCs) without the disadvantages, such as the painful and invasive harvesting procedure, of MSCs derived from bone marrow or adipose tissue. In the present study, we investigated whether the angiogenic efficacy of CBMSCs can be enhanced by grafting as spheroids in a mouse hindlimb ischemia model. Human CBMSC (hCBMSC) spheroids were prepared by using the hanging drop method. Mouse hindlimb ischemia was induced by excising the femoral artery and its branches. After surgery, animals were divided into no-treatment, dissociated hCBMSC, and spheroid hCBMSC groups (n=8 per group) and received corresponding hCBMSC treatments. After surgery, the ischemic hindlimbs were monitored for 4 weeks, and then the ischemic hindlimb muscles were harvested for histological analysis. Apoptotic signaling, angiogenesis-related signal pathways, and blood vessel formation were investigated in vitro and/or in vivo. The transplantation of hCBMSCs as spheroids into mouse ischemic hindlimbs significantly improved the survival of the transplanted cells by suppressing apoptotic signaling while activating anti-apoptotic signaling. Furthermore, the transplantation of hCBMSCs as spheroids significantly increased the number of microvessels and SM a-actin positive vessels in the ischemic limbs of mice, and attenuated limb loss and necrosis. hCBMNC can be an alternative source of MSC and spheroid-based CBMSC delivery can be a simple and effective strategy for enhancing the therapeutic efficacy of CBMSCs