PMID- 27743903
OWN - NLM
STAT- MEDLINE
DCOM- 20170209
LR  - 20231111
IS  - 2352-3964 (Electronic)
IS  - 2352-3964 (Linking)
VI  - 12
DP  - 2016 Oct
TI  - Allogeneic Mesenchymal Precursor Cells (MPC) in Diabetic Nephropathy: A 
      Randomized, Placebo-controlled, Dose Escalation Study.
PG  - 263-269
LID - S2352-3964(16)30418-2 [pii]
LID - 10.1016/j.ebiom.2016.09.011 [doi]
AB  - BACKGROUND: Diabetic nephropathy is the most common cause of end stage renal 
      failure. We assessed the safety, tolerability, and explored therapeutic effects 
      of adult allogeneic bone-marrow derived mesenchymal precursor cells (MPC) in 
      patients with moderate to severe diabetic nephropathy. METHODS: Multicenter, 
      randomized, double-blind, dose-escalating, sequential, placebo-controlled trial 
      assessing a single intravenous (IV) infusion of allogeneic MPC (United States 
      adopted name: rexlemestrocel-L) 150x10(6) (n=10), 300x10(6) (n=10) or placebo 
      (n=10) in adults with diabetic nephropathy with an estimated glomerular 
      filtration rate (eGFR) 20-50ml/min/1.73m(2). Thirty patients at three Australian 
      centers were enrolled between July 2013 and June 2014 and randomized 2:1, in two 
      sequential dose cohorts, to receive rexlemestrocel-L or placebo. Study duration 
      was 60weeks. Primary endpoint was safety and tolerability. Primary exploratory 
      efficacy endpoint was change from baseline in eGFR and directly measured GFR by 
      (99)Tc-DTPA plasma clearance (mGFR) at 12weeks post-infusion. The trial was 
      registered on ClinicalTrials.gov (NCT01843387). FINDINGS: All patients completed 
      the study and were included in analyses applied to the intention to treat 
      population. There were no acute adverse events (AEs) associated with infusion and 
      no treatment-related AEs or serious AEs were deemed treatment-related by 
      investigators. No patients developed persistent donor specific anti-HLA 
      antibodies. Relative to placebo, a single IV rexlemestrocel-L infusion showed 
      trends of stabilizing or improving eGFR and mGFR at week 12. The adjusted least 
      squares mean (LSM+/-SE) differences from placebo in changes from baseline at 
      12weeks in the rexlemestrocel-L groups were 4.4+/-2.16 and 1.6+/-2.15ml/min/1.73m(2) 
      for eGFR and 4.1+/-2.75 and 3.9+/-2.75 for mGFR for the 150x10(6) and 300x10(6) cell 
      groups, respectively. INTERPRETATION: This study demonstrates the safety of 
      rexlemestrocel-L in diabetic nephropathy with suggestive effects on renal 
      function to be confirmed in larger, appropriately powered trials.
CI  - Copyright (c) 2016 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Packham, David K
AU  - Packham DK
AD  - Melbourne Renal Research Group, Melbourne, Victoria, Australia; Department of 
      Medicine, University of Melbourne, Melbourne, Victoria, Australia. Electronic 
      address: dmpackham@netspace.net.au.
FAU - Fraser, Ian R
AU  - Fraser IR
AD  - Epworth Medical Centre, Richmond, Victoria, Australia.
FAU - Kerr, Peter G
AU  - Kerr PG
AD  - Monash Medical Center, Clayton, Victoria, Australia; Monash University, Clayton, 
      Victoria, Australia.
FAU - Segal, Karen R
AU  - Segal KR
AD  - Mesoblast, Inc., New York, NY, United States.
LA  - eng
SI  - ClinicalTrials.gov/NCT01843387
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20160917
PL  - Netherlands
TA  - EBioMedicine
JT  - EBioMedicine
JID - 101647039
SB  - IM
MH  - Aged
MH  - Diabetic Nephropathies/physiopathology/*therapy
MH  - Female
MH  - Glomerular Filtration Rate
MH  - Humans
MH  - Male
MH  - *Mesenchymal Stem Cell Transplantation/adverse effects/methods
MH  - Mesenchymal Stem Cells/*cytology
MH  - Middle Aged
MH  - Transplantation, Homologous
MH  - Treatment Outcome
MH  - Urinalysis
PMC - PMC5078602
OTO - NOTNLM
OT  - Diabetic nephropathy
OT  - Glomerular filtration rate
OT  - Inflammation
OT  - Mesenchymal precursor cells
OT  - Stem cell
EDAT- 2016/10/26 06:00
MHDA- 2017/02/10 06:00
PMCR- 2016/09/17
CRDT- 2016/10/17 06:00
PHST- 2016/08/13 00:00 [received]
PHST- 2016/09/09 00:00 [revised]
PHST- 2016/09/12 00:00 [accepted]
PHST- 2016/10/26 06:00 [pubmed]
PHST- 2017/02/10 06:00 [medline]
PHST- 2016/10/17 06:00 [entrez]
PHST- 2016/09/17 00:00 [pmc-release]
AID - S2352-3964(16)30418-2 [pii]
AID - 10.1016/j.ebiom.2016.09.011 [doi]
PST - ppublish
SO  - EBioMedicine. 2016 Oct;12:263-269. doi: 10.1016/j.ebiom.2016.09.011. Epub 2016 
      Sep 17.