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Abnormal Proliferation and Defective Multilineage differentiation Potential of Adipose‐Derived Stem Cells Isolated from Dystrophin and Utrophin Knockout Mice
Author(s) -
Sohn Jihee,
Kozemchak Adam,
Oyster Nick,
Thompson Seth Davis,
Lu Aiping,
Gharaibeh Burhan,
Tang Ying,
Wang Bing,
Huard Johnny
Publication year - 2012
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.26.1_supplement.914.6
Subject(s) - utrophin , dystrophin , cd44 , stem cell , cd34 , adipose tissue , myogenesis , adipogenesis , microbiology and biotechnology , duchenne muscular dystrophy , chondrogenesis , biology , mesenchymal stem cell , pathology , chemistry , medicine , endocrinology , cell , myocyte , genetics
Adipose derived stem cells (ADSCs) hold potential in cell therapy for a variety of musculoskeletal injuries and diseases including Duchenne Muscular Dystrophy (DMD). DMD is a genetic disease characterized by progressive weakening of the skeletal, cardiac, and diaphragmatic muscles. Using double knock‐out mice (dKO) for dystrophin and utrophin which is a DMD model that better emulates the human phenotype of the disease in mice, we determine if ADSCs from dKO mice are affected in their proliferation and differentiation capacities compared to wild type (WT) ADSCs. ADSCs were isolated from fat tissue of 6 week old dKO‐homo (dys−/−utro−/−), dKO‐hetero (dys−/−utro+/−) and C57BL WT mice and flow cytometry was used to confirm positive expressions of Sca‐1, CD34, CD44 and CD29. Cell proliferation and apoptotic rates investigated using a Live Cell Imaging system showed dKO ADSCs have a higher proliferation rate than WT cells. This may explain the gradual muscle weakness and pseudohypertrophy observed in DMD. Myogenesis, adipogenesis and chondrogenesis are impaired in dKO ADSCs. Impaired myogenesis observed with dKO cells may be a secondary effect of the increased proliferation observed with those cells. These results suggest a dysfunction in the dKO ADSCs and that blocking the exhaustion of ADSCs and stem cell therapy could be used to modulate adipose tissue formation in the muscles of DMD patients to restore structure and function. Grant Funding Source : NIH