The chiaroscuro stem cell: a unified stem cell theory

Hematopoiesis has been considered hierarchical in nature, but recent data suggest that the system is not hierarchical and is, in fact, quite functionally plastic. Existing data indicate that engraftment and progenitor phenotypes vary inversely with cell cycle transit and that gene expression also varies widely. These observations suggest that there is no progenitor/stem cell hierarchy, but rather a reversible continuum. This may, in turn, be dependent on shifting chromatin and gene expression with cell cycle transit. If the phenotype of these primitive marrow cells changes from engraftable stem cell to progenitor and back to engraftable stem cell with cycle transit, then this suggests that the identity of the engraftable stem cell may be partially masked in nonsynchronized marrow cell populations. A general model indicates a marrow cell that can continually change its surface receptor expression and thus responds to external stimuli differently at different points in the cell cycle.     

肠道干细胞

引言干细胞具有自我更新能力和向多种分化的潜能,其中造血干细胞向多种血细胞分化及造血干细胞移植对某些血液病的治疗作用已被认识和熟悉,近年来研究认为,肠道也存在干细胞,且肠道干细胞研究取得了一些进展,肠道干细胞可分化为肠上皮的所有细胞系,参与正常肠黏膜组织更新的生理过程及一些病理过程.迄今国内对肠道干细胞的研究报道较少,本文复习了近年来国外有关肠道干细胞研究的文献并综述如下:     

胰腺干细胞

引言近年研究发现,成年胰腺中存在干细胞,胰腺干细胞能分化形成胰腺导管、胰岛及胰腺外分泌腺泡等特定的胰腺组织细胞,并具有无限分裂和自我更新能力胰腺干细胞属未分化细胞,可表达干细胞的一些分子     

肝干细胞

干细胞是指组织中最原始的具有多潜能性、自我更新的细胞,但不同于组织中的一些前体细胞。虽然前体细胞也具有自我更新能力,但自我更新时间较为短暂。目前通常将干细胞分为三类：①全能干细胞：如胚胎干细胞可以分化形成所有的成体组织细胞,甚至发育成完整个体。②多能干细胞：具有多向分化潜能,可以分化形成除自身组织细胞外的其他组织细胞,如造血干细胞、间充质干细胞和肝干细胞等。③专能干细胞：维持某一特定组织细胞的自我更新,如肠上皮干细胞等。     

Embryonic stem cell

Mouse embryonic stem (ES) cells are the cells that possess pluripotential differentiation activity into not only all somatic cells but also germ cells. Genetic alteration of mouse ES cells can be easily achieved and such genetic modification can be introduced into the animal, since ES cells are differentiated into germ cells in vivo. This technology enables us to analyze the function of any particular genes of interest in mice. And in vitro differentiation induction of mouse ES cells into various cell lineages, such as blood cells, neural cells, and cardiac muscle cells, has been studied. In vitro hematopoietic differentiation experiments were carried out most extensively and can be regarded as a model system of induction. Recently, human ES cells have been established. Many scientists, clinicians and even mass media have entertained the idea that human ES cells can be used after changing the cells into lineage-specific stem cells or progenitor cells such as hematopoietic stem cells and neural progenitor cells.     

Risk assessment in haematopoietic stem cell transplantation: stem cell source

Bone marrow (BM) has been used for many years as the unique source of progenitor cells for allogeneic transplantation. However, two other sources of progenitor cells, peripheral blood (PB) and umbilical cord (UC), are being increasingly used. The type of graft is one of the most important factors in determining the speed and robustness of the reconstitution after the transplant of monocytes, T lymphocytes, B lymphocytes, NK cells, and dendritic cells. This fact is of especial relevance since the most important reactions after allogeneic transplants - e.g. graft-versus-host disease (GVHD), graft-versus-leukaemia effect (GvL), achievement of full donor chimerism, and fight against infections - are strongly influenced by a rapid and robust reconstitution of these cells. For this reason, the choice of the type of graft for allogeneic transplantation will influence the clinical outcome.     

Intestinal stem cell transplantation

Journal of Gastroenterology - Organoid technologies to expand intestinal epithelial cells are gaining increasing attention as a useful tool to investigate many aspects of intestinal epithelial...     

Spermatogonial stem cell transplantation

The development of the spermatogonial transplantation technique has given new impetus to research on spermatogonial stem cells. Possibilities opened by this technique include: (a) New ways to study fundamental aspects of spermatogenesis; (b) Generation of transgenic large domestic animals; (c) Protection of (young) male cancer patients from infertility due to chemotherapy or radiotherapy. Spermatogonial stem cell transplantation for the above purposes encompasses a number of steps. First, the stem cells have to be isolated and possibly purified. Second, it should be possible to cryopreserve the stem cells, for example till the children have reached puberty. Third. it should be possible to culture spermatogonial stem cells for a prolonged period of time which would also allow transfection and subsequent selection of stably transfected cells. Fourth, in case of animal studies. the host testis should be emptied from endogenous stem cells. This is probably best done by local irradiation. Finally, the stem cells will have to be transplanted.     

Haploidentical stem cell transplantation

The feasibility of stem cell transplantation across the major histocompatibility barrier-as in haploidentical stem cell transplantation-has been proved for some time in several studies. The main limitations include a higher graft failure rate, delayed immune reconstitution after transplantation with high rates of life-threatening infections, a higher incidence of post-transplant lymphoproliferative disease, and severe acute and chronic graft-versus-host disease. In an attempt to reduce the transplant-related morbidity/mortality, several techniques had been evaluated involving conditioning regimen intensity, graft engineering, post-transplant cellular therapy and immunosuppression. This review will describe the current situation. It will also discuss initiatives and strategies to overcome the limitations associated with transplant across the MHC barrier.     

Mesenchymal stem cell aging

Stem cells are located throughout the adult body of higher organisms, supporting a continuous renewal and repair of tissues. Unique abilities of stem cells are self-renewal and multipotential differentiation. It is, therefore, of critical importance for an organism to maintain and control quantity and quality of stem cells within a given pool. Otherwise, when something goes awry within a stem cell, it is likely to have far-reaching effects.

Mesenchymal stem cells (MSC) derived from various sources such as bone marrow or fat have been expanded in culture and differentiated in vitro into several lineages such as adipocytes, osteocytes or chondrocytes. In particular, aged human MSC show a decline in differentiation potential as well as in proliferation rate. The latter most likely reflects the fact that aged MSC suffer from eroded telomeres. Besides the individual age of the cell, stem and progenitor cell functions are influenced by the cellular environment, i.e. the niche and the architecture of the tissue, they reside in. This contribution reviews current knowledge about MSC aging (in vitro or in vivo), and respective difficulties for tissue engineering and stem cell therapy.     

The stem cell movement

Stem or progenitor cell-based strategies to combat ischemic heart disease and myocardial infarction, whether autologous transplantation or stimulation of resident populations, not only require detailed insight into transdifferentiation potential and functional coupling, but the efficacy of this approach is underpinned by the need to induce appropriate migration and homing to the site of injury. This review focuses on existing insights into the trafficking of stem cells in the context of cardiac regenerative therapy, with particular focus on the wide variety of potential sources of cells, critical factors that may regulate their migration, and how extrapolating from embryonic stem/progenitor cell behavior during cardiogenesis may reveal pathways implicit in the adult heart postinjury.     

The leukemic stem cell

Malignant stem cells have recently been described as the source of several types of human cancer. These unique cell types are typically rare and possess properties that are distinct from most other tumor cells. The properties of leukemic stem cells indicate that current chemotherapy drugs will not be effective. The use of current cytotoxic agents is not effective in leukemia because the agents target both the leukemic and normal stem cell populations. Consequently, new strategies are required that specifically and preferentially target the malignant stem cell population, while sparing normal stem cells. Several well known agents are lethal for the leukemic stem cell in preclinical testing. They include parthenolide, commonly known as feverfew, and TDZD-8. They have undergone various levels of preclinical development, but have not been used in patients as yet in the cancer setting. These drugs and combinations of existing therapies that target the leukemic stem cell population may provide a cure in this disease. This article summarizes recent findings in the leukemic stem cell field and discusses new directions for therapy.     

Circulating stem cell autografts

The role of autologous bone marrow transplantation in the treatment of malignant disease is currently being evaluated. The peripheral blood represents an alternative source of haemopoietic progenitors and the use of circulating rather than bone marrow stem cells permits autografting in patients with infiltrated bone marrows. It may also offer a lower risk of tumour contamination, although this is not yet proven. Several autografts using circulating stem cells (CSCs) have recently been reported. These are reviewed and current uncertainties and future prospects are discussed.