Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®): preclinical and clinical trial in osteoarthritis of the knee joint.

BACKGROUND: Osteoarthritis (OA) is a common and debilitating chronic degenerative disease of the joints. Currently, cell-based therapy is being explored to address the repair of damaged articular cartilage in the knee joint. METHODS: The in vitro differentiation potential of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®) was determined by differentiating the cells toward the chondrogenic lineage and quantifying sulfated glycosaminoglycan (sGAG). The mono-iodoacetate (MIA)-induced preclinical model of OA has been used to demonstrate pain reduction and cartilage formation. In the clinical study, 60 OA patients were randomized to receive different doses of cells (25, 50, 75, or 150 million cells) or placebo. Stempeucel® was administered by intra-articular (IA) injection into the knee joint, followed by 2 ml hyaluronic acid (20 mg). Subjective evaluations-visual analog scale (VAS) for pain, intermittent and constant osteoarthritis pain (ICOAP), and Western Ontario and McMaster Universities Osteoarthritis (WOMAC-OA) index-were performed at baseline and at 1, 3, 6, and 12 months of follow-up. Magnetic resonance imaging of the knee was performed at baseline, and at 6 and 12 months follow-up for cartilage evaluation. RESULTS: Stempeucel® differentiated into the chondrogenic lineage in vitro with downregulation of Sox9 and upregulation of Col2A genes. Furthermore, Stempeucel® differentiated into chondrocytes and synthesized a significant amount of sGAG (30 ± 1.8 µg/µg GAG/DNA). In the preclinical model of OA, Stempeucel® reduced pain significantly and also repaired damaged articular cartilage in rats. In the clinical study, IA administration of Stempeucel® was safe, and a trend towards improvement was seen in the 25-million-cell dose group in all subjective parameters (VAS, ICOAP, andWOMAC-OA scores), although this was not statistically significant when compared to placebo. Adverse events were predominant in the higher dose groups (50, 75, and 150 million cells). Knee pain and swelling were the most common adverse events. The whole-organ magnetic resonance imaging score of the knee did not reveal any difference from baseline and the placebo group. CONCLUSION: Intra-articular administration of Stempeucel® is safe. A twenty-five-million-cell dose may be the most effective among the doses tested for pain reduction. Clinical studies with a larger patient population are required to demonstrate a robust therapeutic efficacy of Stempeucel® in OA. TRIAL REGISTRATION: Clinicaltrials.gov NCT01453738 . Registered 13 October 2011.

Optimization of the inventory size of the public cord blood program--the Indian context.

BACKGROUND: There are reportedly more than 250,000 cord blood units [CBU] available in cord blood banks world over, yet, there are many who are unable to get a suitable match. Being the pioneer to set up the first and only public cord blood bank in India, we needed to strategize the pool size that will meet the transplantation needs of the people of Indian origin, worldwide. PURPOSE: To define the optimum size of this public cord blood repository [CBR] that will give at least one 5/6 HLA match to a defined number of cord blood graft requests. METHODS: We checked the trend of human Leukocyte antigen [HLA] match graft offerings, to 112 random requests from a database of 1800 CBUs. The HLA match function was performed using an 'in house' built and validated software. The pattern of availability of the matches was used as the basis of our study. We then performed a probability analysis to check the probable pool size that would offer at least one acceptable match to all the 112 requests. RESULTS: With an inventory of 1800 units, we could offer 4/6 matches to about 99% and 5/6 matches to approximately only 29% and 6/6 matches to only 7% of the 112 random requests. Thus, acceptable matches were offered to about 30% of the requests received in the period and database considered for this study. CONCLUSION: By employing probability analysis, we concluded that, by doubling the size, we will probably offer at least one 5/6 match to each requester, and from a pool size of about 55500 grafts, we may offer a full house (6/6 match) to the same number of requisitions. Genetic homology between the recipient and donor base, increases the probability of match availability. A good ethnic representation of the Indian population in our CBR plays a significant role in match availability.