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 regeneration.

Wurmser, Andrew E; Palmer, Theo D; Gage, Fred H

Science (Washington) [Science (Wash.)]. Vol. 304, no. 5675, pp. 1253-1255. 28 May 2004.

Stem 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.).

Zhu, Jiang; Emerson, Stephen G

Bioessays [Bioessays]. Vol. 26, no. 6, pp. 595-599. 2004.

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.

Wakayama, T

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 technology.

Khavari, PA

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.

Elisseeff, JH

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.

Fuchs, E; Tumbar, T; Guasch, G

Cell [Cell]. Vol. 116, no. 6, pp. 769-778. Mar 2004.

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.

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 transplantation.

Morshead, CM; Van der Kooy, D

Current Opinion in Neurobiology [Curr. Opin. Neurobiol.]. Vol. 14, no. 1, pp. 125-131. Feb 2004.

A description 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.

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. Feb 2004.

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.

Ema, H; Nakauchi, H

Immunity [Immunity]. Vol. 20, no. 1, pp. 1-2. Jan 2004.

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.