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3.3.2 Hematopoietic cells
Hematopoietic stem cells are multipotent cells comprising blood
components from both myeloid and lymphoid lineages. Autologous
and allogeneic donor harvested hematopoietic stem cells are currently
used clinically to treat some forms of cancer and immune system dis-
orders (hematopoietic stem cell transplantation). One issue facing this
therapy is the limited availability of human leukocyte antigen compat-
ible hematopoietic stem cells. These cells are difficult to harvest and
expand and in the case of allogeneic transplant, there is risk of tissue
rejection or graft-versus-host disease. Generation of hematopoietic
cells from hPSCs could provide an infinite source of these cells. In the
case of iPSCs, a hematopoietic stem cell transplant could serve as an
alternative autograph cell source.
In 2001, Kaufman et al. differentiated hESCs to hematopoietic
progenitors expressing cell surface marker CD34 by coculture with
murine bone marrow cells or yolk sac endothelial cells.^61 This method
did not require any exogenous growth factors, but did use fetal
bovine serum.^61 For clinical applications this method is not practical
due to its lack of definition and reliance on murine coculture. In
2009, Choi et al. published a differentiation protocol using OP9
coculture to derive CD34 and CD43 positive hematopoietic progeni-
tors from hESCs and iPSCs.^62 Again, this technique was not ideal as
it involved a coculture with stromal cells reducing the clinical applica-
tions of this technique and the resulting cells.
In 2003, Chadwick et al. published the first hematopoietic
differentiation protocol demonstrating the role of cytokines in pro-
moting hematopoietic lineage definition as marked by the expression
of CD45.^63 They used hESCs in an embryoid body culture and sup-
plemented with stem cell factor (SCF), Flt-3 ligand, interleukin-3,
interleukin-6, granulocyte colony stimulating factor, and BMP4.^63
Although they identified BMP4 did not play a significant role in
hematopoietic differentiation, BMP4 treatment without cytokines
enhanced progenitor proliferation.^63 Interestingly, in 2007, Pick et al.
explored the roles of several different cytokines (VEGF, SCF, BMP4,
and FGF2) in inducing hematopoietic differentiation in human
embryoid body culture conditions without serum or coculture.^64
