PMID- 25311054
OWN - NLM
STAT- MEDLINE
DCOM- 20151110
LR  - 20220310
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 5
IP  - 5
DP  - 2014 Oct 13
TI  - Pre-clinical studies of bone regeneration with human bone marrow stromal cells 
      and biphasic calcium phosphate.
PG  - 114
LID - 10.1186/scrt504 [doi]
LID - 114
AB  - INTRODUCTION: Repair of large bone defects remains a significant clinical 
      challenge. Bone marrow stromal cells (BMSCs), a subset of which is known as bone 
      marrow-derived mesenchymal stem cells, show therapeutic potential for bone 
      regeneration. However, their isolation, expansion and implantation will need to 
      be conducted under good manufacturing practices (GMP) at separate locations. An 
      investigation which mimics this clinical scenario where large bone defects shall 
      be regenerated is required before clinical trials can be initiated. METHODS: 
      Seven batches of 100 million human ex-vivo expanded BMSCs from five donors were 
      transported fresh in syringes from a GMP facility in Germany to France. BMSCs 
      were mixed with biphasic calcium phosphate (BCP) biomaterial prior to 
      subcutaneous implantation in nude mice. The capacity of BMSCs in unison with BCP 
      to regenerate critical sized cranial bone defects was also evaluated. BMSCs 
      expressing luciferase were used to assess the viability and bio-distribution of 
      implanted cells. In situ hybridization, using the human-specific repetitive Alu 
      sequence, was performed for the identification of human cells in explants. 
      RESULTS: Eight weeks after implantation of BMSCs, mineralized bone containing 
      mature bone marrow territories was formed in ectopic sites and in calvaria 
      defects. Significant loss of cell viability was observed by bioluminescence 
      imaging and only 1.5 percent of the initial number of transplanted cells remained 
      after 37 days. After eight weeks, while explants were comprised primarily of host 
      cells, there were also human cells attached along the periphery of BCP and 
      embedded in osteocyte lacunae dispersed throughout the newly formed bone matrix. 
      CONCLUSIONS: This study demonstrates the safety and efficacy of BMSC/BCP 
      combinations and provides crucial information for the implementation of BMSC 
      therapy for bone regeneration.
FAU - Brennan, Meadhbh A
AU  - Brennan MA
FAU - Renaud, Audrey
AU  - Renaud A
FAU - Amiaud, Jerome
AU  - Amiaud J
FAU - Rojewski, Markus T
AU  - Rojewski MT
FAU - Schrezenmeier, Hubert
AU  - Schrezenmeier H
FAU - Heymann, Dominique
AU  - Heymann D
FAU - Trichet, Valerie
AU  - Trichet V
FAU - Layrolle, Pierre
AU  - Layrolle P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141013
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 0 (Calcium Phosphates)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Bone Regeneration/*drug effects
MH  - Calcium Phosphates/*pharmacology
MH  - Cell Differentiation/drug effects
MH  - Female
MH  - Humans
MH  - Mesenchymal Stem Cells/*cytology/*drug effects
MH  - Mice
MH  - Mice, Nude
MH  - Random Allocation
MH  - Young Adult
PMC - PMC4445278
EDAT- 2014/10/15 06:00
MHDA- 2015/11/11 06:00
PMCR- 2014/10/13
CRDT- 2014/10/15 06:00
PHST- 2014/05/21 00:00 [received]
PHST- 2014/09/30 00:00 [accepted]
PHST- 2014/10/15 06:00 [entrez]
PHST- 2014/10/15 06:00 [pubmed]
PHST- 2015/11/11 06:00 [medline]
PHST- 2014/10/13 00:00 [pmc-release]
AID - scrt504 [pii]
AID - 428 [pii]
AID - 10.1186/scrt504 [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2014 Oct 13;5(5):114. doi: 10.1186/scrt504.