Buerger's disease or thromboangiitis obliterans is a type of obstructive vascular diseases categorized as vasculitis and usually present in 95% of young smoker men. The main pathogenetic mechanism is interplay between immune system and inflammation. Earlier our phase II study has shown that Stempeucel is safe when injected at 2 million cells/kg body weight by virtue of its anti-inflammatory, immunomodulatory, and angiogenetic properties. The present study was conducted to further assess the safety and efficacy of Stempeucel in critical limb ischemia due to Buerger's disease after obtaining approval from Indian FDA based on the data generated in the phase II study. This is an open label, multicenteric phase IV PMS study conducted across India with experienced vascular surgeons. Fifty patients of critical limb ischemia due to Buerger's disease with Rutherford III-5 or III-6 were included in the study and each individual received a dose of 2 million cells/kg body weight of Stempeucel in the calf muscles and around the ulcer. These patients were evaluated over 12 months from drug administration. The present study showed the continued long term efficacy over a period of 12 months follow up in these patients corroborating the result obtained in the previous phase II studies. There was significant improvement in rest pain, ankle systolic pressure, and ankle brachial pressure index with accelerated ulcer healing. In conclusion, the present study shows that the intramuscular administration of Stempeucel continues to be safe, tolerable, and effective alternative treatment in patients with Buerger's disease.

Background Peripheral arterial disease (PAD) of lower extremities comprises a clinical spectrum that extends from asymptomatic patients to critical limb ischemia (CLI) patients. 10% to 40% of the patients are at the risk of primary amputation. This study was planned in “no-option” patients of CLI due to atherosclerotic PAD to assess the efficacy and safety of pooled, allogeneic, adult human bone marrow-derived mesenchymal stromal cells which is already approved for marketing in India for CLI due to Buerger’s disease. Methods This was a single-arm, multi-centric, phase III study where mesenchymal stromal cells was injected as 2 million cells/kg body weight in the calf muscle and around the ulcer. Twenty-four patients of lower extremity CLI due to PAD with Rutherford III-5 or III-6 and ankle–brachial pressure index ≤ 0.6 and having have at least one ulcer with area between 0.5 and 10 cm2 were included in the study. These patients were evaluated over 12 months from drug administration. Results Over a period of 12 months, statistical significant reduction of rest pain and ulcer size along with improvement in ankle–brachial pressure index and ankle systolic was observed. The quality of life of patients improved together with increase in total walking distance and major amputation-free survival time. Conclusion Mesenchymal stromal cells may be a feasible option to treat “no-option” patients with atherosclerotic PAD. Trial registration This study is registered prospectively in National Institutes of Health and Clinical Trials Registry—India (CTRI) website: CTRI/2018/06/014436. Registered 6th June 2018. http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=24050&EncHid=&userName=stempeutics.

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Background: Alcoholic liver cirrhosis is an end-stage alcoholic liver disease with a poor prognosis. The definitive treatment of alcoholic liver cirrhosis is orthotopic liver transplantation, which is expensive, requires long-term immunosuppression and is limited by the supply of organs. Being an unmet medical need, cell therapy is under investigation for alcoholic liver cirrhosis. Aims: This study was designed primarily for assessing the safety and feasibility of administering stempeucel® through the hepatic artery in alcoholic liver cirrhosis and secondarily to assess possible efficacy and dose-response. Methods: Sixty patients with alcoholic cirrhosis (18-65 years/Child-Pugh class B or C/Model for End-Stage Liver Disease score of minimum 10) were planned to be included in 6 groups: 2.5 million cells/kg Body Weight (2.5M Cell) and respective control (2.5M Control); 5 million cells/kg Body Weight (5M Cell) and respective control (5M Control); 7.5 million cells/kg Body Weight (5M Cell) and respective control (7.5M Control) with 10 patients in each group. Cell groups received stempeucel® administered via hepatic artery by catheterization through the femoral artery (Seldinger technique) and Standard Protocol of Care. The control group received Standard Protocol of Care. Patients were followed up at 1 week, 1 month, 3 months and 6 months. Efficacy evaluations included liver function test, Model for End-Stage Liver Disease score, Child-Pugh score, Short Form-36 questionnaire, liver stiffness using Fibroscan (Transient Elastography), and liver volume using Computerized Tomography scan. Results: Stempeucel® injection was well tolerated. Common treatment-emergent adverse events were gastrointestinal disorders, general disorders and administration site conditions and infections and infestations. Most of the treatment-emergent adverse events were unrelated / remotely related to stempeucel®. Thirty serious adverse events occurred in 10 patients (3 in 2.5M Cell, 5 in 5M Cell and one each in control groups). Three patients died due to SAEs: Two in 2.5M and one in 5M Cell group, none were related to stempeucel®. Statistically significant improvement was seen in 2.5M group compared to the control group in Short Form-36 score: bodily pain, mental component summary, vitality and social functioning. Conclusion: Stempeucel® was safe, well-tolerated and subjective improvement in Short Form-36 (bodily pain, mental component summary, vitality and social functioning and mental health) score was seen in the 2.5M cell group.

Background: Alcoholic liver cirrhosis is an end stage alcoholic liver disease with poor prognosis. The definitive treatment of alcoholic liver cirrhosis is orthotopic liver transplantation, which is expensive, requires long term immunosuppression and is limited by supply of organs. Being an unmet medical need, cell therapy is under investigation for alcoholic liver cirrhosis.Aims: This study was designed primarily for assessing the safety and feasibility of administering stempeucel® through the hepatic artery in alcoholic liver cirrhosis and secondarily to assess possible efficacy and dose-response.Methods: Forty patients with alcoholic cirrhosis (18-65 years/Child Pugh class B or C/Model for End-Stage Liver Disease score of minimum 10) were included in 4 groups: 2.5 million cells/kg Body Weight (2.5M Cell) and respective control (2.5M Control); 5 million cells/kg Body Weight (5M Cell) and respective control (5M Control) with 10 patients in each group. Cell groups received stempeucel® administered via hepatic artery by catheterization through femoral artery (Seldinger technique) and Standard Protocol of Care. Control group received Standard Protocol of Care. Patients were followed up at 1 week, 1 month, 3 months and 6 months. Safety evaluations included clinical examination, Electrocardiogram and laboratory investigations. Efficacy evaluations included liver function test, Model for End-Stage Liver Disease score, Child Pugh score, Short Form-36 questionnaire, liver stiffness using Fibroscan (Transient Elastography), and liver volume using Computerized Tomography scan. Results: stempeucel® injection was well tolerated. Common treatment emergent adverse events were in Gastrointestinal disorders, General disorders and administration site conditions and Infections and infestations. Most of the treatment emergent adverse events were unrelated / remotely related to stempeucel®. Thirty serious adverse events occurred in 10 patients (3 in 2.5M Cell, 5 in 5M Cell and one each in control groups). Three patients died due to SAEs: Two in 2.5M and one in 5M Cell group, none were related to stempeucel®. There was no significant difference in efficacy evaluations at 6 months versus baseline compared to control at both the dose levels of stempeucel®. Statistically significant improvement was seen in 2.5M group compared to control group in Short Form-36 score: bodily pain, mental component summary, vitality and social functioning. Conclusions: stempeucel® was safe, well tolerated and subjective improvement in few component scores of Short Form-36 was seen 2.5M cell group.Trial registrationClinicaltrials.gov: NCT01591200Clinical Trial Registry – India: CTRI/2009/091/000432