Primate skeletal muscle contains cells capable of sustaining in vitro hematopoiesis

Several investigators recently reported that adult murine skeletal muscle cells possess a remarkable capacity to differentiate into hematopoietic cells. We further examined this biologic process by studying the phenotype and in vitro functional behavior of primate skeletal muscle cells.

Muscles from human abortuses as well as fetal and adult baboons were digested enzymatically and mononuclear cell fractions were isolated. Muscle tissue-derived mononuclear cells (mu-TDMNC) were phenotypically characterized. Both short-term and long-term hematopoietic progenitors were assayed from mu-TDMNC using standard techniques. Gene expression patterns characteristic of hematopoietic and endothelial cells were examined in primary and cultured muscle cells.

Primate muscle cells were shown to express the CD34 antigen. Such CD34(+) cells were shown to be CD45(-) and desmin(+), indicating they were not of hematopoietic origin. Fetal but not adult muscle cells contained assayable hematopoietic progenitors. In addition, muscles contained an additional class of progenitors that formed colonies composed of blast cells after prolonged incubation (3-4 weeks). A two-step culture system was established that permitted muscle cells to continue to proliferate when exposed to a hematopoietic environment for 8 months. During this prolonged period of time, the generation of CD34(+), CD56(+), CD11b(+), and CD31(+) as well as von Willebrand factor (vWF)(+) cells were observed.

Our studies indicate that although primate muscle cells contain a significant number of CD34(+) cells, they are likely not of hematopoietic origin. Important ontogenic differences in the hematopoietic potential of primate muscle cells were documented. When exposed to appropriate microenvironmental stimuli, mu-TDMNC displayed an extensive proliferative capacity and contained primitive progenitors with the capacity to generate cells in vitro with phenotypic and genetic properties of hematopoietic and endothelial cells for sustained periods of time. Whether this observation can be accounted for by true transdifferentiation of muscle cells or proliferation of reservoirs of hematopoietic and endothelial progenitor cells residing within skeletal muscle remains unresolved.