PMID- 21895491
OWN - NLM
STAT- MEDLINE
DCOM- 20120716
LR  - 20211020
IS  - 1937-3392 (Electronic)
IS  - 1937-3384 (Print)
IS  - 1937-3384 (Linking)
VI  - 17
IP  - 12
DP  - 2011 Dec
TI  - Toward a clinical-grade expansion of mesenchymal stem cells from human sources: a 
      microcarrier-based culture system under xeno-free conditions.
PG  - 1201-10
LID - 10.1089/ten.tec.2011.0255 [doi]
AB  - The immunomodulatory properties of mesenchymal stem cells (MSCs) make them 
      attractive therapeutic agents for a wide range of diseases. However, the highly 
      demanding cell doses used in MSC clinical trials (up to millions of cells/kg 
      patient) currently require labor intensive methods and incur high reagent costs. 
      Moreover, the use of xenogenic (xeno) serum-containing media represents a risk of 
      contamination and raises safety concerns. Bioreactor systems in combination with 
      novel xeno-free medium formulations represent a viable alternative to 
      reproducibly achieve a safe and reliable MSC doses relevant for cell therapy. The 
      main goal of the present study was to develop a complete xeno-free 
      microcarrier-based culture system for the efficient expansion of human MSC from 
      two different sources, human bone marrow (BM), and adipose tissue. After 14 days 
      of culture in spinner flasks, BM MSC reached a maximum cell density of 
      (2.0+/-0.2)x10(5) cells.mL(-)(1) (18+/-1-fold increase), whereas adipose tissue-derived 
      stem cells expanded to (1.4+/-0.5)x10(5) cells.mL(-)(1) (14+/-7-fold increase). After the 
      expansion, MSC expressed the characteristic markers CD73, CD90, and CD105, 
      whereas negative for CD80 and human leukocyte antigen (HLA)-DR. Expanded cells 
      maintained the ability to differentiate robustly into osteoblast, adipocyte, and 
      chondroblast lineages upon directed differentiation. These results demonstrated 
      the feasibility of expanding human MSC in a scalable microcarrier-based stirred 
      culture system under xeno-free conditions and represent an important step forward 
      for the implementation of a Good Manufacturing Practices-compliant large-scale 
      production system of MSC for cellular therapy.
FAU - Santos, Francisco dos
AU  - Santos Fd
AD  - Department of Bioengineering, Instituto Superior Tecnico-IST, Lisboa, Portugal.
FAU - Andrade, Pedro Z
AU  - Andrade PZ
FAU - Abecasis, Manuel M
AU  - Abecasis MM
FAU - Gimble, Jeffrey M
AU  - Gimble JM
FAU - Chase, Lucas G
AU  - Chase LG
FAU - Campbell, Andrew M
AU  - Campbell AM
FAU - Boucher, Shayne
AU  - Boucher S
FAU - Vemuri, Mohan C
AU  - Vemuri MC
FAU - Silva, Claudia Lobato da
AU  - Silva CL
FAU - Cabral, Joaquim M S
AU  - Cabral JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110906
PL  - United States
TA  - Tissue Eng Part C Methods
JT  - Tissue engineering. Part C, Methods
JID - 101466663
RN  - 0 (Culture Media)
RN  - 0 (Plastics)
SB  - IM
MH  - Adipose Tissue/cytology
MH  - Adult
MH  - Animals
MH  - Bone Marrow Cells/cytology/drug effects/metabolism
MH  - Cell Culture Techniques/*methods
MH  - Cell Lineage/drug effects
MH  - Cell Proliferation/drug effects
MH  - Culture Media/pharmacology
MH  - Humans
MH  - Immunophenotyping
MH  - Mesenchymal Stem Cells/*cytology/drug effects/metabolism
MH  - *Microspheres
MH  - Plastics
PMC - PMC3226421
EDAT- 2011/09/08 06:00
MHDA- 2012/07/17 06:00
PMCR- 2012/12/01
CRDT- 2011/09/08 06:00
PHST- 2011/09/08 06:00 [entrez]
PHST- 2011/09/08 06:00 [pubmed]
PHST- 2012/07/17 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - 10.1089/ten.tec.2011.0255 [pii]
AID - 10.1089/ten.tec.2011.0255 [doi]
PST - ppublish
SO  - Tissue Eng Part C Methods. 2011 Dec;17(12):1201-10. doi: 
      10.1089/ten.tec.2011.0255. Epub 2011 Sep 6.