Clinical trial using a combination of autologous bone marrow and umbilical cord blood derived mesenchymal stem cells in

1. Dr. Meghana Kanitkar, Dr. Sachin Jamadar and Dr. Anant Bagul. Chaitanya Stem Cell Centre, Pune, M.S., INDIA, www.chaitanyastemcell.com ABSTRACT AND INTRODUCTION Stroke is a brain disorder that renders patients severely impaired and permanently disabled. Currently, there are no known treatments for reversing these deficits. The use of autologous bone marrow derived mononuclear cells (MNCs) and umbilical cord blood derived mesenchymal stem cells (UCMSCs) have been documented as treatment in such disorders. However, these treatment regimes display limited and delayed results – thus loosing valuable treatment and recovery time. To overcome this limitation, we have used a combination of MNCs (100 x106 / dose) and UCMSCs (10x 106 / dose) in three doses, intra thecally, into 5 adult males. Subjects were assessed for improvement in the following areas: reduction in spasticity, ataxia, muscle power, mental and social behavior and overall functional ability using various applicable scales. It was observed that treatment with a combination of both cell types caused reduction in spasticity, increase in muscle power and improvement in social behavior at a faster rate than that achieved by UCMSCs or MNCs alone. Our results are preliminary experimental / clinical evidence to prove that combination therapy with MNCs and UCMSCs is safe and efficacious in enhancing patient recovery rate. The upcoming third dose may yield even more exiting results. Post this ‘first evidence’, extensive research will have to be carried out before more concrete claims can be made for usage of this technique as therapy. Experimental design 5 adult males, between the age groups of 25 to 50 yrs, with internal capsule injury in the corona radiata region leading to stroke and who were all suffering from stroke for at least 2.5 yrs were chosen for this experimental therapy. Grp 1 was treated with 3 doses of UCMSCs (10 x 106 cells / dose), Grp 2 was treated with 3 doses of autologous bone marrow derived MNCs (100 x 106 / dose). Grp 3 was administered a combination of both at each dose. All doses were administered intra-thecally at a time interval of 30 days. Detailed follow-up revealed the following results. RESULTS Increase in muscle power % decrease of falls in stroke patients Figure depicts increase in muscle power achieved over 3 doses of UCMSCs, MNCs, or combination of both. Blue line- UCMSCs;Green line- MNCs;Yellow line- combination. The Ashworth scale was used for grading muscle spasticity. Figure depicts % decrease in falls in stroke patients achieved due to 3 doses of UCMSCs, MNCs, or combination of both. Blue column- UCMSCs;Green column- MNCs;Yellow column- combination. No Social Behavior UCMSc MNCs Combi nation SUMMARY: • Combination therapy caused significant improvement in muscle power as opposed to treatment with MNCs or UCMSCs alone. • Treatment with combination therapy also caused significant reduction in spasticity as opposed to MNCs or UCMSCs alone. • One of the 5 patients showed especial improvement in his ability to stand without support. Originally he was able to stand unsupported for 5 to 6 mins which improved to 11 to 12 min after combination therapy. No other results of such nature were observed in any of the other treatment or control groups. • There was also marked increase in social responses and reduction in aggressiveness in patients exposed to combination therapy while such responses were not observed in patients treated with MNCs or UCMSCs alone. • No adverse effects or incidences were observed in any of the control or experimental groups. 1. Reduction in Aggression ---- ---- + + 2. Anxiety ---- ---- + + 3. Emotional Quotient ---- ---- + + 4. Irritability ---- ---- + + 5. Sleeping patterns ---- ---- + + CONCLUSION: A combination of UCMSCs and MNCs may prove to be a safer and more efficacious treatment alternative in case of stroke as compared to either of the treatments alone. However this will have to be further validated with extensive research. Clinical trial using a combination of autologous bone marrow and umbilical cord blood derived mesenchymal stem cells in patients with stroke. 30.21 % 23. 31% 26.42 %