PMID- 26153271
OWN - NLM
STAT- MEDLINE
DCOM- 20160405
LR  - 20220409
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Print)
IS  - 0149-5992 (Linking)
VI  - 38
IP  - 9
DP  - 2015 Sep
TI  - Allogeneic Mesenchymal Precursor Cells in Type 2 Diabetes: A Randomized, 
      Placebo-Controlled, Dose-Escalation Safety and Tolerability Pilot Study.
PG  - 1742-9
LID - 10.2337/dc14-2830 [doi]
AB  - 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. RESEARCH DESIGN AND METHODS: The study was a 
      dose-escalating randomized placebo-controlled trial assessing one intravenous 
      (IV) infusion of MPCs (rexlemestrocel-L; Mesoblast Inc.) 0.3 x 10(6)/kg (n = 15), 
      1.0 x 10(6)/kg (n = 15), or 2.0 x 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 x 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 x 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.
CI  - (c) 2015 by the American Diabetes Association. Readers may use this article as long 
      as the work is properly cited, the use is educational and not for profit, and the 
      work is not altered.
FAU - Skyler, Jay S
AU  - Skyler JS
AD  - Diabetes Research Institute, University of Miami, Miami, FL 
      jskyler@med.miami.edu.
FAU - Fonseca, Vivian A
AU  - Fonseca VA
AD  - Tulane University Health Sciences Center, New Orleans, LA.
FAU - Segal, Karen R
AU  - Segal KR
AD  - Mesoblast Inc., New York, NY.
FAU - Rosenstock, Julio
AU  - Rosenstock J
AD  - Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX.
CN  - MSB-DM003 Investigators
LA  - eng
SI  - ClinicalTrials.gov/NCT01576328
GR  - U54 GM104940/GM/NIGMS NIH HHS/United States
GR  - 1U54-GM-104940/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150707
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Adult
MH  - Blood Glucose
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Hypoglycemia/chemically induced/prevention & control
MH  - Hypoglycemic Agents/*administration & dosage/adverse effects
MH  - Male
MH  - Mesenchymal Stem Cells/*drug effects
MH  - Metformin/*administration & dosage/adverse effects
MH  - Middle Aged
MH  - Pilot Projects
MH  - Treatment Outcome
PMC - PMC4542273
EDAT- 2015/07/15 06:00
MHDA- 2016/04/06 06:00
PMCR- 2016/09/01
CRDT- 2015/07/09 06:00
PHST- 2014/11/28 00:00 [received]
PHST- 2015/06/09 00:00 [accepted]
PHST- 2015/07/09 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2016/04/06 06:00 [medline]
PHST- 2016/09/01 00:00 [pmc-release]
AID - dc14-2830 [pii]
AID - 2830 [pii]
AID - 10.2337/dc14-2830 [doi]
PST - ppublish
SO  - Diabetes Care. 2015 Sep;38(9):1742-9. doi: 10.2337/dc14-2830. Epub 2015 Jul 7.