A role for chemistry in stem cell biology
Ding, Sheng; Schultz, Peter G
Nature Biotechnology [Nat. Biotechnol.].
Vol. 22, no. 7, pp. 833-840. Jul 2004.
Although stem cells hold
considerable promise for the treatment of numerous diseases including
cardiovascular disease, neurodegenerative disease, musculoskeletal disease,
diabetes and cancer, obstacles such as the control of stem cell fate,
allogenic rejection and limited cell availability must be overcome before
their therapeutic potential can be realized. This requires an improved
understanding of the signaling pathways that affect stem cell fate.
Cell-based phenotypic and pathway-specific screens of natural products and
synthetic compounds have recently provided a number of small molecules that
can be used to selectively control stem cell proliferation and
differentiation. Examples include the selective induction of neurogenesis
and cardiomyogenesis in murine embryonic stem cells, osteogenesis in
mesenchymal stem cells and dedifferentiation in skeletal muscle cells. Such
molecules will likely provide new insights into stem cell biology, and may
ultimately contribute to effective medicines for tissue repair and
Cellular Interactions in the Stem Cell Niche
Wurmser, Andrew E; Palmer, Theo D; Gage, Fred H
[Science (Wash.)]. Vol. 304, no. 5675, pp. 1253-1255. 28 May 2004.
cells are capable of both self-renewal and differentiation into many
different cell types. These hallmark characteristics are regulated by other
cells within the stem cell niche. In their Perspective, Wurmser et al.
discuss the finding that endothelial cells in the neural stem cell niche
secrete factors that influence neural stem cells to proliferate and become
neurons (Shen et al.).
A new bone to pick: osteoblasts and the haematopoietic stem-cell
Zhu, Jiang; Emerson, Stephen G
Bioessays [Bioessays]. Vol. 26, no. 6, pp.
Two recent publications highlight the role of bone-forming
cells, the osteoblasts, in controlling the development of neighboring
haematopoietic stem cells (HSCs). Using two distinct transgenic mouse
models, one using the conditional deletion of the Bone Morphogenetic
Protein Receptor 1A (BMPR1A) gene, the other using over-expression of an
active PTH/PTHrP receptor (PPR) mutant within osteoblasts, the authors show
parallel, concordant increases in the generation of trabecular osteoblasts
and the number of HSCs. In situ staining showed that rarely cycling HSCs
sporadically attach to endosteal osteoblasts, while in vitro assays
indicated that ligation of Jag1 on osteoblasts by Notch1 on HSCs promotes
HSC proliferation. These two independent works have revived and revitalized
the notion that osteoblasts are a major, defining component of the HSC
niche within the bone marrow (BM). This minireview discusses these results
in the context of other recent studies of mesenchymal cells within the BM
microenvironment, presents one potential unified model of the functional
anatomy of the BM HSC niche, and highlights new questions raised by these
and other studies of osteoblasts and HSCs.
On the road to therapeutic cloning
Nature Biotechnology [Nat. Biotechnol.]. Vol. 22, no. 4, pp.
399-400. Apr 2004.
Human embryonic stem (ES) cells have been derived from
cloned embryos, an important step in the development of therapeutic
cloning. The political tussles surrounding human ES cells have overshadowed
discussion of the scientific challenges that lie ahead if the promise of ES
cells for regenerative medicine is to be realized. A recent report by Hwang
et al. in Science of ES-cell derivation from a cloned human embryo invites
reflection on the obstacles that remain in the development of this
Profiling epithelial stem cells
Nature Biotechnology [Nat. Biotechnol.]. Vol. 22, no. 4, pp.
393-394. Apr 2004.
Healthy skin and hair follicles depend on the
self-renewal capacity of long-lived stem cells. The definitive
identification and characterization of these cells holds significant
promise for the fields of stem cell biology, tissue regeneration,
transplantation, gene therapy and cancer. In the case of skin, however,
this goal has proven elusive because of a lack of specific markers and the
resulting inability to isolate living epithelial stem cells. Two new
reports, one in this issue and one in Science, surmount this problem using
distinct but complementary strategies that shed light both on the niche
where these cells reside and on the gene expression patterns that
distinguish them from their more differentiated neighbors.
Embryonic stem cells: potential for more impact
Trends in Biotechnology [Trends Biotechnol.]. Vol. 22, no.
4, pp. 155-156. Apr 2004.
Human embryonic stem cells have generated
significant excitement and energy in many areas of biomedical research,
including tissue engineering and regenerative medicine. A recent paper by
the Langer group provides a glimpse into potential future therapeutics and
clinical applications of stem cells in tissue engineering, as well as
giving new insights into how stem cells interact with biomaterials.
Socializing with the Neighbors Stem Cells and Their Niche
Fuchs, E; Tumbar, T; Guasch, G
Cell [Cell]. Vol. 116, no. 6, pp. 769-778.
The potential of stem cells in regenerative medicine relies
upon removing them from their natural habitat, propagating them in culture,
and placing them into a foreign tissue environment. To do so, it is
essential to understand how stem cells interact with their
microenvironment, the so-called stem cell niche, to establish and maintain
their properties. In this review, we examine adult stem cell niches and
their impact on stem cell biology.
The immunogenicity of human embryonic stem-derived cells
Drukker, M; Benvenisty, N
Trends in Biotechnology [Trends Biotechnol.].
Vol. 22, no. 3, pp. 136-141. Mar 2004.
Human embryonic stem cells have
excellent potential for being the ultimate source of transplantable cells
for many different tissues. To enable their clinical use, differentiation
protocols should be developed and safety standards must be met. The cells
should improve symptoms without generating side effects and their immune
rejection must be overcome. Profiling of the immune antigens expressed on
the cells has revealed that upon differentiation the cells express
molecules of the major histocompatibility complex. Here, we propose ways of
overcoming the rejection of human embryonic stem cells after
Disguising adult neural stem cells
Morshead, CM; Van der Kooy, D
Current Opinion in Neurobiology [Curr.
Opin. Neurobiol.]. Vol. 14, no. 1, pp. 125-131. Feb 2004.
of adult neural stem cells has remained somewhat elusive. With no unique
and definitive markers to label stem cells in general, neural stem cells
are difficult to identify definitively and one is forced to examine cell
behavior-- leading to the retrospective identification of a stem cell. The
most prevalent view in the literature describes the adult forebrain neural
stem cell as a relatively quiescent subependymal cell that expresses glial
fibrillary acidic protein. In this review we summarize some of the recent
studies that have supported or challenged this conception of the nature of
the adult forebrain neural stem cell. We highlight and compare the
experimental paradigms that have led to our current state of knowledge and
conclude that there is no reason at present to abandon the prevailing view
of adult neural stem cell identity.
Neural stem cells in the mammalian eye: types and regulation
Ahmad, I*; Das, AV; James, J; Bhattacharya, S; Zhao, X
Seminars in Cell &
Developmental Biology [Semin. Cell Dev. Biol.]. Vol. 15, no. 1, pp. 53-62.
Neural stem cells/progenitors that give rise to neurons and
glia have been identified in different regions of the brain, including the
embryonic retina. Recently, such cells have been reported to be present, in
a mitotically quiescent state, in the ciliary epithelium of the adult
mammalian eye. The retinal and ciliary epithelium stem cells/progenitors
appear to share similar signaling pathways that are emerging as important
regulators of stem cells in general. Yet, they are different in certain
respects, such as in the potential to self-renew. These two neural stem
cell/progenitor populations not only will serve as models for investigating
stem cell biology but also will help explain the relationships between
embryonic and adult neural stem cells/progenitors.
'Homing to Niche, ' a New Criterion for Hematopoietic Stem Cells?
Ema, H; Nakauchi, H
Immunity [Immunity]. Vol. 20, no. 1, pp. 1-2. Jan
By combining cell surface staining with fluorochrome-conjugated
monoclonal antibodies and Hoechst 33342 dye supravital staining, Matsuzaki
et al. have succeeded in enriching hematopoietic stem cells (HSCs)
essentially to homogeneity. When single-cell transplantation analysis was
performed using the isolated cells, over 95% of the recipient mice showed
long-term multilineage engraftment. The work demonstrates unexpectedly high
marrow seeding efficiency of HSCs and proposes high marrow homing capacity
as a new criterion for HSCs.