Biomedical Engineering Reference
In-Depth Information
4.7.3 Bone marrow-derived stem cells and progenitors
Recent studies indicate that in rare circumstances, such as extensive cutaneous
injury, self-renewing subpopulations in the bone marrow are induced to participate
in the healing process, whereby they give rise to collagen-secreting cells that seem
to play a role during wound repair. These two self-renewal subpopulations are (1)
bone marrow-derived mesenchymal stem cells and (2) hematopoietic stem
cells.
12,68,70-86,99,100
Bone marrow (BM) also harbors a progenitor subpopulation
(endothelial progenitor cells) which, in the same type of setting, are mobilized to
aid in the reconstruction of blood vessels.
69,92-98,101-103,107
Moreover, it is thought
that, extensive injury to skin also promotes the early trafficking of a unique
subclass of leukocytes (circulating fibrocytes) to the injured region, where they
perform various functions related to wound healing.
26-32,55,56,88
Bone marrow-derived mesenchymal stem cells (BM-derived MSCs)
The stroma of bone marrow is home to a group of multipotent stem cells,
commonly known as BM-derived MSCs (or simply MSCs.)
10,78,80
MSCs are
responsible for generating progenitors that give rise mainly to stromal cells,
hepatocytes, adipocytes, myocytes, chrondrocytes and osteocytes. Although MSCs
do not generate hematopoietic progenitors, they do give rise to stromal cells that
support the development of HSCs. Several non-specific markers are used to
identify MSCs, including adhesion markers CD44, CD29 and CD90. In addition,
they must not express hematopoietic markers CD34 and CD45.
Despite limited clinical application of MSCs, their potential use in regenerative
medicine has created much interest.
81,82
MSCs may have the ability to suppress T-
cell activation and proliferation and thus could become a potential treatment for
allograft rejection, graft-versus-host disease and autoimmune conditions.
81,83,84
Other potential uses include treatments for myocardial infarction
85
and spinal cord
injury.
86
Hematopoietic stem cells (HSCs)
The other group of multipotent stem cells (found in the BM) is HSCs. Unlike
MSCs, clinical applications of HSCs have been met with some success.
87
They are
used routinely in the treatment of leukemia, lymphoma, inherited blood disorders
(aplastic anemia,
-thalassemia, SCID) and cancer chemotherapy rescue. Al-
though relatively easy to culture, it is not yet known if using cultured HSCs to treat
skin injury is efficacious.
HSCs play a critical role in maintaining the homeostasis of the circulating
system.
87
Accordingly, all hematopoietic subpopulations are replenished by pro-
genitors that originate from HSCs. Markers used to identify human HSCs are
CD34, CD59, Thy-1 and c-kit (low.) Mice HSCs require a different set of markers:
Sca-1, Thy-1, CD38, c-kit and CD34 (low.)
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