Open AccessStem Cell‐Derived Therapeutic Myelin Repair Requires 7% Cell Replacement
Author(s) -
Kiel Mary E.,
Chen Cui P.,
Sadowski Dorota,
McKin Randall D.
Publication year - 2008
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2008-0218
Subject(s) - biology , stem cell , embryonic stem cell , population , myelin , regeneration (biology) , cell , immunology , neuroscience , microbiology and biotechnology , central nervous system , genetics , gene , medicine , environmental health
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. Disclosure of potential conflicts of interest is found at the end of this article.