期刊
STEM CELLS
卷 26, 期 9, 页码 2229-2236出版社
WILEY
DOI: 10.1634/stemcells.2008-0218
关键词
cell transplantation; embryonic stem cells; glia; oligodendrocytes; thresholds
资金
- New Jersey Commission on Spinal Cord [05-3047-SCR-E-0]
- Stem Cell Research [06-2042-014-74]
- National Institute of Mental Health [MH54652]
Embryonic stem cells (ESCs) hold great potential for therapeutic regeneration and repair in many diseases. However, many challenges remain before this can be translated into effective therapy. A principal and significant limit for outcome evaluations of clinical trials is to define the minimal graft population necessary for functional repair. Here we used a preclinical model for quantitative analysis of stem cell grafts, with wild-type ESC grafted into myelin mutant shiverer hosts, to determine minimum graft levels for therapeutic benefit. Using a timed motor function test we identified three groups, including recipients indistinguishable from nongrafted shiverer controls (time [t] = 20.1 +/- 1.1 seconds), mice with marginal improvement (t = 15.7 +/- 1 seconds), and mice with substantial phenotype rescue (t = 5.7 +/- 0.9 seconds). The motor function rescued chimeras also had a considerably extended life span (T-50 > 128 days) relative to both shiverer (T-50 = 108 days) and the nonrescued chimeras. Retrospective genotype analysis identified a strong correlation (r(2) = 0.85) between motor function and ESC-derived chimerism, with > 7% chimerism required for rescue in this murine model of central nervous system myelin pathology. These results establish the minimal levels of engraftment to anticipate therapeutic repair of a cell-autonomous defect by cell transplant therapy.
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