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Stem Cell Culture Engineering

The Stem Cell Project is a collaboration with Prof. Catherine Verfaillie of the Stem Cell Institute at the University of Minnesota, and is based on her discovery that rare multipotent stem cells can be found in the marrow of humans and rodents. These cells, termed Multipotent Adult Progenitor Cells or MAPC, can be expanded in an undifferentiated state for greater than 100 population doublings ex vivo. MAPC differentiate at the single cell level into osteoblasts, chondroblasts, fibroblasts, adipocytes, myoblasts, endothelial cells, neuro-ectodermal cells and hepatocytes in vitro. Human/murine MAPC engraft in non-irradiated recipient mice, where they differentiate in response to local cues to hematopoietic cells, epithelium of lung, liver and the gastrointestinal tract. Human/murine MAPC are recruited to injured tissues, and enhanced engraftment is seen in the hematopoietic and gastrointestinal system when MAPC are infused in irradiated recipients, and MAPC are recruited to areas of neoangiogensis where they contribute to endothelial cells and smooth muscle cells of arterioles. When injected in mouse muscle, human MAPC differentiate into skeletal muscle. Finally, MAPC contribute to all tissues when injected in the blastocyst. MAPC differ from other adult stem cells because they proliferate without senescence, differentiate into functional cells from the three germ layers, contribute to all tissues in the blastocyst, and engraft in vivo in proliferating tissues, including mesodermal and endodermal cell types, in response to local cues. MAPC have characteristics similar to those of embryonic stem (ES) cells, namely proliferation without senescence, single cell differentiation to all three germ layers, and contribution to all somatic cell types when injected in a blastocyst. However, MAPC differ from ES cells in that they engraft in post natal animals and differentiate in response to local cues in a tissue specific manner; no teratoma formation has been seen in vivo. Unlike ES, MAPC for implantation can be derived from the patient, allowing autologous therapies; and engraft in hematopoietic tissues, clearing the way for establishment of hematopoietic chimerism that should enable subsequent tissue specific cell therapy from the same allogeneic donor.

A major challenge in further advancement of MAPC for both research and clinical applications is the undefined and laborious nature of their cultivation. The immediate goals of this program are to unveil the control mechanisms of MAPC growth and differentiation and to develop a culture system for tissue engineering applications.

http://hugroup.cems.umn.edu/Research/Stem%20Cell/stem_cell%20.htm

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