Fabrication of adipose-derived mesenchymal stem cell aggregates using biodegradable porous microspheres for injectable adipose tissue regeneration

Injectable mesenchymal stem cell aggregates were formed using hyaluronic acid (HA)-immobilized porous biodegradable microspheres for adipose tissue regeneration. Adipose tissue-derived mesenchymal stem cells (AMSCs) were aggregated in a controlled manner and differentiated into adipocytes by cultivating in a stirred suspension bioreactor. The resultant cellular aggregates were approx. 1700 μm in diameter and exhibited fully differentiated adipocytes, as shown by immunocytochemistry and RT-PCR. The cultured aggregates could be smoothly injected into the subcutaneous region of mice through a syringe needle due to their soft elasticity and deformability. The in vivo regenerated adipose tissue maintained a proper dimension and shape, showing natural adipose tissue characteristics, as demonstrated by various histological staining procedures. HA-immobilized microspheres significantly enhanced cell differentiation during 3D cultivation, and tissue regeneration when implanted in vivo, compared to unmodified porous microspheres. This study showed that AMSC cellular aggregates prepared by using porous microspheres could be delivered in an injectable manner into the body and could have great therapeutic potential for soft tissue augmentation and reconstruction.