Osteoarthritis (OA) tends to occur in older individuals frequently burdened with comorbidities and diverse pharmacological interactions. As articular cartilage has low regenerative power, potent local tissue engineering approaches are needed to support chondrogenic differentiation. Acellular preparation methods as well as approaches to coax endogenous reparative cells into the joint space appear to have limited success. Supported by our in-vitro and clinical studies, we propose that our novel intra-articular administration of human granulocyte colony stimulating factor (IA-hG-CSF) combined with autologous activated peripheral blood stem cells (AAPBSC) is safe and offers treatment advantages not seen with other cellular interventions in early osteoarthritis.