Umbilical cord blood cell transplantation for myocardial regeneration

Bone marrow remains the most frequently used source of adult stem cells, but its angiogenic and possibly also myogenic potentials are likely to regress with increasing donor age and morbidity. Recently, cord blood has been suggested as a readily available source for non-embryonic stem cells with high regenerative capacity. We first tested the capacity of mononuclear cells obtained from human umbilical cord blood (UCB(mn)) to migrate to the heart on IV delivery in NOD/Scid mice. As evidenced by the presence of human DNA by PCR analysis, UCB(mn) cells migrated to the heart in 50% of the mice with myocardial infarctions, but in none of the sham-operated control mice. In UCB(mn) cell-positive injured hearts, the infarct size was smaller and capillary density higher in the ischemic myocardium. By immunohistology, we observed endothelial cell differentiation of UCB(mn) cells in the heart but there was no colocalization of UCB cell-specific antibodies with markers of myocyte-type cells. In a second series of experiments, we injected 5 x 10(5) UCB cells enriched for CD133 directly into the necrotic myocardium of NOD/Scid mice. Comparisons were performed with an equivalent number of CD133+ bone marrow (BM) cells or a sham injection in the respective control groups. Both BMCD133+ and UCBCD133+ cells abolished postoperative mortality and improved capillary density in the injured myocardium, but only BMCD133+ cells led to a detectable improvement in myocardial contractility in vivo. We conclude that human UCB cells facilitated neovascularization of ischemic myocardium, but their capacity for formation of contractile neotissue needs further investigation.     

Stem cell research and transplantation: science leading ethics

One of the most exciting developments in the biological sciences in the past decade has been the discovery and characterization of human embryonic stem cells (ESCs). The interest to transplanters is the potential applications of stem cells in regenerative medicine (RM), which may involve tissue engineering, genetic engineering, and other techniques to repair, replace, or regenerate failing tissues and organs. There is little controversy surrounding human adult stem cells. However, human ESCs are surrounded by a number of ethical controversies, the extent of which is partly dependent on their source. Those derived from currently existing embryonic stem cell lines are less controversial than those derived from "excess" embryos from in vitro fertilization (IVF) clinics, while ESCs derived from IVF embryos specifically created for the purpose are not acceptable to many people arguing from religious and other moral perspectives. Somatic cell nuclear transfer, or therapeutic cloning, must be distinguished from reproductive cloning. It holds the most promise for regenerative medicine. ESCs can also be derived from gonadal ridges of aborted fetuses. The transplant community must strive to uphold societal values in its effort to find remedies for their ailing patients and address the perennial problem of organ shortage. Transplanters also have a responsibility to engage the public in their efforts to gain public understanding and support, and policy makers must take into account public opinion. Only in this way can we realize the great potential of stem cell research for organ transplantation.     

Stem cell research in cell transplantation: sources, geopolitical influence, and transplantation

If the rapidly progressing field of stem cell research reaches its full potential, successful treatments and enhanced understanding of many diseases are the likely results. However, the full potential of stem cell science will only be reached if all possible avenues can be explored and on a worldwide scale. Until 2009, the US had a highly restrictive policy on obtaining cells from human embryos and fetal tissue, a policy that pushed research toward the use of adult-derived cells. Currently, US policy is still in flux, and retrospective analysis does show the US lagging behind the rest of the world in the proportional increase in embryonic/fetal stem cell research. The majority of US studies being on either a limited number of cell lines, or on cells derived elsewhere (or funded by other sources than Federal) rather than on freshly isolated embryonic or fetal material. Neural, mesenchymal, and the mixed stem cell mononuclear fraction are the most commonly investigated types, which can generally be classified as adult-derived stem cells, although roughly half of the neural stem cells are fetal derived. Other types, such as embryonic and fat-derived stem cells, are increasing in their prominence, suggesting that new types of stem cells are still being pursued. Sixty percent of the reported stem cell studies involved transplantation, of which over three quarters were allogeneic transplants. A high proportion of the cardiovascular systems articles were on allogeneic transplants in a number of different species, including several autologous studies. A number of pharmaceutical grade stem cell products have also recently been tested and reported on. Stem cell research shows considerable promise for the treatment of a number of disorders, some of which have entered clinical trials; over the next few years it will be interesting to see how these treatments progress in the clinic.     

干细胞与肾脏再生

干细胞研究是一项新兴研究，在一些领域已应用于临床治疗疾病。在肾脏疾病尤其急性肾损伤修复方面，干细胞也显示了巨大的应用前景。研究显示多种干细胞可参与肾损伤后修复和肾脏再生。本文对近年来关于干细胞和肾损伤修复、肾脏再生的文献进行了回顾。     

干细胞移植治疗下肢重度缺血

下肢重度缺血是指下肢动脉闭塞性病变引起下肢的静息痛、溃疡和(或)坏疽,具有较高的致残率和致死率。目前,导致下肢重度缺血的主要疾病有下肢动脉硬化闭塞症和血栓闭塞性脉管炎,其中作为下肢动脉硬化闭塞症特殊类型的糖尿病下肢缺血导致的重度缺血日益受到重视。尽管随着传统外科技术和血管腔内治疗技术的进步,下肢动脉缺血的治疗效果得到提高,但下肢重度缺血的治疗一直是血管外科医师面临的主要难题之一[1]。目前临     

Stem cell regeneration of the intervertebral disk

The use of stem cell applications has been explored and aimed at regenerating the intervertebral disk. The microenvironment in which cells of the intervertebral disk reside is harsh; however, researchers have reported on many applications for stem cells, including research aimed at defining and stimulating endogenous stem cell populations, methods to induce stem cell differentiation toward intervertebral disk cell phenotype in vivo, and direct transplantation of stem cells into damaged intervertebral disk to promote transplanted site-dependant differentiation. Successful results have been reported, although limitations remain. This article reviews the current status of stem cell research as applied to the intervertebral disk.     

干细胞治疗与肾脏病研究

干细胞是一类可以自我更新、多向分化和高度增殖的细胞。由于干细胞的可塑性、无限扩增性、便于遗传操作等优势,干细胞疗法为现代医学提供了一个新的治疗途径。近年来干细胞治疗在肝病、肿瘤疾病、血液疾病等各个研究领域逐步发展和广泛应用,同样也为肾脏疾病治疗学的研究带来了新的契机。故本文针对干细胞生物学基础、干细胞治疗与肾脏病研究及其目前所面临的主要问题等方面作一综述。     

Stem cell transplantation: the lung barrier

BACKGROUND: Mesenchymal stem cells (MSCs) show differentiation capacity along mesenchymal lineages and have the potential to aid tissue regeneration. MSC transplantation strategies are therefore currently being assessed following injury to various organs. However, potential MSC migration to these organs after intravenous (IV) MSC injection continues to be impeded by cell trapping within the lung. METHODS: Mouse MSCs were isolated, purified, transfected with firefly luciferase, and labeled with CSFE. Their size was assessed in vitro. To estimate the diameter of mouse pulmonary capillaries, fluorescence-labeled microspheres of different sizes were injected with or without sodium nitroprusside (SN) pretreatment. The lungs were harvested after 30 seconds and mean numbers of trapped microspheres per high-power field (HPF) were calculated. After IV injection of MSC suspensions (with or without SN), their dynamic distribution was monitored by in vivo luciferine imaging as well as by histopathology. RESULTS: The diameter of suspended MSCs in vitro was 15 to 19 microm. Whereas nearly no 4-microm microspheres could be detected in lung sections, the numbers of trapped 10- and 15-microm microspheres could be significantly decreased by prior SN injection from 19.3 +/- 11.1 to 6.0 +/- 1.6 cells/HPF (P = .004) and from 34.9 +/- 11.9 to 25.6 +/- 8.1 cells/HPF (P = .028), respectively. Within seconds after MSC IV injection, the vast majority of cells was found in the lungs. However, cell trapping in the pulmonary microvasculature was significantly reduced by pre-treatment with SN. CONCLUSIONS: We demonstrate that cell trapping in lungs can be reduced with IV SN pretreatment, increasing MSC passage through the lung capillaries, and potentially facilitating cell access to injured organs.     

Stem cell transplantation eliminates alloantibody in a highly sensitized patient.

Highly sensitized patients are forced to stay on transplant waiting lists for many years and ultimately may never find a donor. Peripheral blood stem cell (PBSC) transplantation may provide a strategy to decrease host alloreactivity through the production of a chimeric state. We investigated alloreactivity and chimerism in a highly sensitized 40-year-old patient with sickle cell disease who underwent a nonradiation based conditioning regimen consisting of fludarabine, ATG, and high dose melphalan, for allogeneic stem cell transplant. Host monocytes and lymphocytes became donor in origin by day 14. PRA, initially 100% pretransplant, fell to 0 by day 263. Anti-red blood cells antibody became undetectable by day 152. The use of a new nonradiation-based conditioning regimen enabled successful engraftment of allogeneic donor PBSCs and the elimination of alloantibody. As new less toxic conditioning regimens are developed, PBSC transplantation might provide a new solution to allosensitization.     

Stem cell transplantation as a therapeutic strategy for traumatic brain injury

Stem cell transplantation has enormous potential to be a viable therapeutic approach to replace the lost tissue/cells following traumatic brain injury (TBI). Several types of cell lines such as immortalized progenitors cells, embryonic rodent and human stem cells and bone marrow-derived cells have been successfully transplanted in experimental models of TBI, resulting in reduced neurobehavioral deficits and attenuation of histological damage. To date, it remains unclear whether stem cell are effective following transplantation into the injured brain via either cell replacement, trophic support, or manipulation of the local environment to stimulate endogenous neuroprotection/regeneration. This paper will review the most current and exciting pre-clinical data regarding the utility of cellular transplantation in experimental models of TBI. We believe that further work must continue to better understand the interaction between the host and the transplanted cells as well as the mechanisms regulating their differentiation into mature and functionally active neurons/glia.