Microenvironmental considerations in the application of human mesenchymal stem cells in regenerative therapies.
The therapeutic utilization of stem cells has been ongoing for several decades, principally in the form of bone marrow (BM) transplants to treat various hematological disorders and other immune-related diseases. More recently, stem cells have been examined as a potential therapy for a multitude of other diseases and disorders, many of which are currently untreatable. One consideration that poses a formidable task for the successful clinical application of stem cells in new disease models is the impact of the host tissue microenvironment on the desired therapeutic outcome. In vitro, stem cells exist in surroundings directly controllable by the researcher to produce the desired cellular behavior. In vivo, the transplanted cells are exposed to a dynamic host microenvironment laden with soluble mediators and immunoreactive cells. In this review, we focus on the possible contribution by microenvironmental factors, and how these influences can be overcome in therapies utilizing mesenchymal stem cells (MSCs), such as for graft versus host disease, multiple sclerosis and ischemia among others. Specifically, we examine three ubiquitous microenvironmental factors, IL-1alpha/beta(,) TNFalpha, and SDF-1alpha, and consider how inhibitors and receptor antagonists to these molecules could be applied to increase the efficacy of MSC therapies while minimizing unforeseen harm to the patient.
Greco
Steven J
SJ
Graduate School of Biomedical Sciences.
Rameshwar
Pranela
P
J Exp Med. 1996 Sep 1;184(3):1101-9
9064327
Adv Immunol. 1993;54:167-227
8379462
Tissue Eng. 2007 Nov;13(11):2615-24
17961003
Cytotherapy. 2007;9(1):69-79
17361488
Biochem Biophys Res Commun. 2005 May 20;330(4):1299-305
15823584
Stem Cells. 2007 Jul;25(7):1737-45
17395768
J Immunol. 2007 Sep 1;179(5):3342-50
17709551
Stem Cells. 2007 Nov;25(11):2896-902
17901396
Front Biosci. 2007 Sep 01;12:4946-56
17569622
Eur J Haematol. 2006 Jun;76(6):488-93
16494621
FASEB J. 2007 Oct;21(12):3197-207
17496162
Front Biosci. 2004 May 01;9:1782-93
14977586
Stem Cells. 2006 Aug;24(8):1976-85
16644922
Exp Hematol. 2000 Aug;28(8):875-84
10989188
Mol Immunol. 1993 Nov;30(16):1443-53
8232330
Stem Cells. 2001;19(3):180-92
11359943
Cell Biol Int. 2006 May;30(5):466-71
16630729
Brain Res. 2008 Feb 21;1195:104-12
18206136
Blood Rev. 2005 Nov;19(6):321-31
16275420
Mol Cell Neurosci. 2007 Jan;34(1):59-68
17113786
N Engl J Med. 2001 Mar 22;344(12):907-16
11259725
Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11002-7
17569781
J Virol. 1999 Feb;73(2):1719-23
9882387
Stem Cells. 2005 Mar;23(3):383-91
15749933
Stem Cells. 2007 Nov;25(11):2797-808
17656644
J Immunol. 2003 Oct 1;171(7):3426-34
14500637
Biochem Biophys Res Commun. 2006 Jul 7;345(3):1167-76
16713999
Future Oncol. 2007 Feb;3(1):19-27
17280498
Biomaterials. 2006 Aug;27(22):4087-97
16616366
Oncogene. 2004 May 6;23(21):3770-80
15034548
Cell. 2001 Feb 23;104(4):487-501
11239407
Stem Cells. 2007 Dec;25(12):3143-54
17761754
Expert Opin Investig Drugs. 2000 Jan;9(1):113-27
11060665
Stem Cells Dev. 2007 Oct;16(5):811-26
17999602
FASEB J. 1994 Dec;8(15):1314-25
8001745
Clin Cancer Res. 2003 Aug 1;9(8):3115-23
12912963
Rheum Dis Clin North Am. 1998 Aug;24(3):615-28
9710890
Nature. 1990 Jan 25;343(6256):336-40
2137200