title: Allogeneic Mesenchymal Precursor Cells in Type 2 Diabetes: A Randomized, Placebo-Controlled, Dose-Escalation Safety and Tolerability Pilot Study.
abstract: OBJECTIVE
  To assess the safety, tolerability, and feasibility of adult allogeneic bone marrow-derived mesenchymal precursor cells (MPCs) in type 2 diabetes inadequately controlled with metformin either alone or with one additional oral antidiabetic agent.
  
  
  METHODS
  The study was a dose-escalating randomized placebo-controlled trial assessing one intravenous (IV) infusion of MPCs (rexlemestrocel-L; Mesoblast Inc.) 0.3 × 10(6)/kg (n = 15), 1.0 × 10(6)/kg (n = 15), or 2.0 × 10(6)/kg (n = 15) or placebo (n = 16). Study duration was 12 weeks.
  
  
  RESULTS
  Subjects (21 women, 40 men) with a mean ± SD baseline HbA1c 8.3 ± 1.0% (67 ± 10.9 mmol/mol), BMI 33.5 ± 5.5 kg/m(2), and diabetes duration 10.1 ± 6.0 years were enrolled at 18 U.S. sites. No acute adverse events (AEs) were associated with infusion. No serious AEs, serious hypoglycemia AEs, or discontinuations due to AEs over 12 weeks were found. No subjects developed donor-specific anti-HLA antibodies or became sensitized. The safety profile was comparable among treatment groups. Compared with placebo, a single IV infusion of rexlemestrocel-L reduced HbA1c at all time points after week 1. The adjusted least squares mean ± SE dose-related differences in HbA1c from placebo in the rexlemestrocel-L groups ranged from -0.1 ± 0.2% (-1.1 ± 2.2 mmol/mol) to -0.4 ± 0.2% (4.4 ± 2.2 mmol/mol) at 8 weeks and from 0.0 ± 0.25% to -0.3 ± 0.25% (-3.3 ± -2.7 mmol/mol) at 12 weeks (P < 0.05 for 2.0 × 10(6)/kg dose at 8 weeks). The clinical target HbA1c <7% (53 mmol/mol) was achieved by 33% (5 of 15) of the subjects who received the 2.0 × 10(6)/kg dose vs. 0% of those who received placebo (P < 0.05).
  
  
  CONCLUSIONS
  This short-term study demonstrates the safety and feasibility of up to 246 million MPCs in subjects with type 2 diabetes.
authors.affiliation: Diabetes Research Institute, University of Miami, Miami, FL jskyler@med.miami.edu.
authors.forename: Jay S
authors.initials: JS
authors.lastname: Skyler
authors.affiliation: Tulane University Health Sciences Center, New Orleans, LA.
authors.forename: Vivian A
authors.initials: VA
authors.lastname: Fonseca
authors.affiliation: Mesoblast Inc., New York, NY.
authors.forename: Karen R
authors.initials: KR
authors.lastname: Segal
authors.affiliation: Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX.
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
mesh_terms: D000328:Adult; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008687:Metformin