Electrostatic crosslinked in situ-forming in vivo scaffold for rat bone marrow mesenchymal stem cells

We herein formulated and characterized an in situ-forming gel consisting of sodium carboxymethylcellulose (CMC) and poly(ethyleneimine) (PEI) and examined its use as an in vivo scaffold for rat bone marrow stem cells (rBMSCs). The changes of zeta potential, size, and viscosity of CMC solutions with 0 to 30 wt% PEI confirmed the electrostatic interaction and temperature-dependence between anionic CMC and cationic PEI. The CMC/PEI solution produced an electrostatically crosslinked gel with a three-dimensional network structure. The CMC solution containing 10 wt% PEI transformed to a gel at temperatures greater than 35 degrees C and was chosen for subcutaneous injection into rats. The CMC/PEI (90/10) gel with pore structure acted as a suitable biocompatible substrate for the in vitro and in vivo attachment and proliferation of rBMSCs. As the CMC/PEI (90/10) solution with and without rBMSCs was injected into Fisher rats, it became a gel in the subcutaneous dorsum of the rats and maintained its shape even after 28 days in vivo. The injected rBMSCs survived in the CMC gel for 28 days. Injection of CMC/PEI gel alone induced macrophage accumulation in the host tissue and at the edge of the gel, whereas injection of CMC/PEI gel containing rBMSCs was associated with less macrophage accumulation, indicating immunosuppression by the transplanted rBMSCs. Our results collectively show that CMC/PEI gel could serve as an in situ-forming gel scaffold for entrapped rBMSCs in vivo.