title: Administration of Adult Human Bone Marrow-Derived, Cultured, Pooled, Allogeneic Mesenchymal Stromal Cells in Critical Limb Ischemia Due to Buerger's Disease: Phase II Study Report Suggests Clinical Efficacy.
abstract: Critical limb ischemia (CLI) due to Buerger's disease is a major unmet medical need with a high incidence of morbidity. This phase II, prospective, nonrandomized, open-label, multicentric, dose-ranging study was conducted to assess the efficacy and safety of i.m. injection of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (BMMSC) in CLI due to Buerger's disease. Patients were allocated to three groups: 1 and 2 million cells/kg body weight (36 patients each) and standard of care (SOC) (18 patients). BMMSCs were administered as 40-60 injections in the calf muscle and locally, around the ulcer. Most patients were young (age range, 38-42 years) and ex-smokers, and all patients had at least one ulcer. Both the primary endpoints-reduction in rest pain (0.3 units per month [SE, 0.13]) and healing of ulcers (11% decrease in size per month [SE, 0.05])-were significantly better in the group receiving 2 million cells/kg body weight than in the SOC arm. Improvement in secondary endpoints, such as ankle brachial pressure index (0.03 [SE, 0.01] unit increase per month) and total walking distance (1.03 [SE, 0.02] times higher per month), were also significant in the group receiving 2 million cells/kg as compared with the SOC arm. Adverse events reported were remotely related or unrelated to BMMSCs. In conclusion, i.m. administration of BMMSC at a dose of 2 million cells/kg showed clinical benefit and may be the best regimen in patients with CLI due to Buerger's disease. However, further randomized controlled trials are required to confirm the most appropriate dose. Stem Cells Translational Medicine 2017;6:689-699.
authors.affiliation: Stempeutics Research, Bangalore, India.
authors.forename: Pawan K
authors.initials: PK
authors.lastname: Gupta
authors.affiliation: Department of Vascular Surgery, Sri Jayadeva Institute of Cardiovascular Sciences, Bangalore, India.
authors.forename: Murali
authors.initials: M
authors.lastname: Krishna
authors.affiliation: Stempeutics Research, Bangalore, India.
authors.forename: Anoop
authors.initials: A
authors.lastname: Chullikana
authors.affiliation: Department of Vascular Surgery, MS Ramaiah Medical College & Hospitals, Bangalore, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Desai
authors.affiliation: Department of Vascular Surgery, SRM Medical College, Chennai, India.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Murugesan
authors.affiliation: Department of Cardiovascular Surgery, Nightingale Hospital, Kolkata, India.
authors.forename: Santanu
authors.initials: S
authors.lastname: Dutta
authors.affiliation: Department of Cardiovascular Surgery, Health Point Hospital, Kolkata, India.
authors.forename: Uday
authors.initials: U
authors.lastname: Sarkar
authors.affiliation: Department of Vascular Surgery, Sri Ramachandra Medical College, Chennai, India.
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Raju
authors.affiliation: Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Dhar
authors.affiliation: Division of Peripheral Vascular and Endovascular Sciences, Medanta-The Medicity, Gurgaon, Haryana, India.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Parakh
authors.affiliation: Department of Biostatistics, Christian Medical College, Vellore, India.
authors.forename: Lakshmanan
authors.initials: L
authors.lastname: Jeyaseelan
authors.affiliation: Stempeutics Research, Bangalore, India.
authors.forename: Pachaiyappan
authors.initials: P
authors.lastname: Viswanathan
authors.affiliation: Stempeutics Research, Bangalore, India.
authors.forename: Prasanth Kulapurathu
authors.initials: PK
authors.lastname: Vellotare
authors.affiliation: Stempeutics Research, Bangalore, India.
authors.forename: Raviraja N
authors.initials: RN
authors.lastname: Seetharam
authors.affiliation: Stempeutics Research, Bangalore, India.|Manipal University, Manipal, India.
authors.forename: Charan
authors.initials: C
authors.lastname: Thej
authors.affiliation: Stempeutics Research, Bangalore, India.
authors.forename: Mathiyazhagan
authors.initials: M
authors.lastname: Rengasamy
authors.affiliation: Stempeutics Research, Bangalore, India.
authors.forename: Sudha
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: Stempeutics Research, Bangalore, India.
authors.forename: Anish S
authors.initials: AS
authors.lastname: Majumdar
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002478:Cells, Cultured; D005121:Extremities / Q000098:blood supply* / Q000473:pathology; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007511:Ischemia / Q000473:pathology / Q000628:therapy*; D018810:Magnetic Resonance Angiography; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D013919:Thromboangiitis Obliterans / Q000473:pathology / Q000628:therapy*; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult
keywords: Bone marrow; Buerger’s disease; Critical limb ischemia; Mesenchymal stromal cells; Stempeucel