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Selective isolation of bone marrow stromal cells residing in the infarcted region of the brain after stroke
Author(s) -
Yilmaz Gokhan,
Alexander Steven J.,
Yilmaz Cigdem Erkuran,
Stokes Karen Y.,
Granger Neil D.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb24-a
Subject(s) - bone marrow , stromal cell , stroke (engine) , cerebral infarction , medicine , pathology , chemistry , immunology , ischemia , mechanical engineering , engineering
The therapeutic potential of exogenous bone marrow stromal cells (BMSC) has been demonstrated in different models of stroke and brain injury. BMSC selectively migrate and home to the site of cerebral injury. Although various techniques have shown that the BMSC reside in or around the site of the cerebral infarct, selective isolation of BMSC from infarct site has not been reported. Our objective was to isolate the BMSC that selectively migrate and home to the infarct site. Stroke was induced in C57BL/6 wild type (WT) mice by middle cerebral artery occlusion for 1 h, followed by 24 h reperfusion. BMSC were isolated either from H‐2Kb‐tsA58 (expresses SV40 large T antigen that allows cell division at 33°C) or from WT mice. BMSC were administered intravenously 24 h after the stroke. Mice were sacrificed 1 week after administration of BMSC. Infarcted hemispheres were removed and treated with 2% collagenase for cell isolation. Isolated cells were cultured at 33°C. Mice that received BMSC from H‐2Kb‐tsA58 showed improvement of neurological function comparable to mice that received BMSC from WT. BMSC from H‐2Kb‐tsA58 were able to grow at 33°C whereas neither the endogenous cerebral cells of the recipient mice nor the BMSC from WT donors were able to grow at this temperature. The use of subpopulations of BMSC derived from thermolabile large‐T transgenic mice that preferentially accumulate at sites of cerebral injury represents a novel and potentially useful strategy for characterizing the therapeutic properties of BMSC in cerebrovascular disease. Supported by R01 HL26441.