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1.
Autoimmune diseases are incurable and are managed using therapeutic agents. Bone marrow transplantation is being trialled as a treatment for these diseases. While allogeneic bone marrow transplantation shows impressive benefit, its application is hindered by GVHD and high mortality. On the other hand, autologous bone marrow transplantation has lower mortality rate and no GVHD but is associated with higher relapse rates. Given that autoimmune diseases are a result of a failure of immune tolerance and that bone marrow-derived dendritic cells play an important role in establishing immune tolerance, the transplantation of genetically modified haematopoietic stem cells to generate molecular chimerism to induce antigen-specific tolerance offers the potential for developing a cure for autoimmune diseases. In this review, we will discuss key findings from clinical data and animal studies to provide evidence to support the above concept. 相似文献
2.
《Bone and mineral》1989,5(2):129-138
Studies involving bone marrow transplantation of osteopetrotic rodents have provided evidence for the lineage of the ostcoclast. Recent investigations have demonstrated that pluripotent hemopoietic stem cells (PHSC) isolated from the bone marrow of normal animals cure the skeletal sclerosis and result in the formation of normal osteoclasts when transplanted into ia osteopetrotic rats. A criticism of these findings is that the microenvironment of the osteopetrotic bone and the bone marrow compartment may be unique in its ability to induce the differentiation of these stem cells into osteoclasts. To test this hypothesis, PHSC were co-cultured with fetal metatarsal bones from normal animals. PHSC were isolated from normal bone marrow using FITC-labelled monoclonal antibodies directed against rat Thy 1.1 and fluorescence-activated cell sorting. The PHSC or whole mononuclear bone marrow were co-cultured with 20-day fetal rat metatarsal rudiments. In some cultures, recombinant mouse granulocyte-macrophage colony-stimulating factor (rGM-CSF) (250 U per culture) was added in addition to the PHSC. After 7 days the fetal bones were prepared for light and electron microscopy and the number of osteoclasts generated in vitro was determined. The PHSC isolate generated as many osteoclasts as the whole mononuclear bone marrow. The addition of rGM-CSF did not enhance the generation of osteoclasts in either control bones or in bones cultured with PHSC. These results are equivalent to those reported in the osteopetrotic transplant system. 相似文献
3.
The osteopetrotic (os) rabbit is a lethal mutation of autosomal recessive inheritance characterized by hypocalcemia, hypophosphatemia, fibrosis of marrow spaces, and ultrastructural abnormalities in both osteoclasts and osteoblasts. Procedures involving the transplantation of cells from normal hemopoietic tissues, which are sources of osteoclast precursors, are known to cure osteopetrosis in several mutations including some children. We tested the ability of transplanted bone marrow and/or spleen from normal littermates to reverse the skeletal sclerosis in os rabbits. Treatment of 15 neonatal mutants consisted of immunosuppression by whole-body irradiation followed by transplantation of normal bone marrow and/or spleen cell suspensions. This treatment failed to prolong life span or to cure osteopetrosis judged radiographically and histologically for up to 3 weeks posttreatment, the longest time of survival. These data indicate that transplantation of stem cells from multiple hemopoietic tissues, procedures known to cure osteopetrosis in other mutations, is not effective in the os rabbit. These results support the hypothesis that the skeletal microenvironment is not capable of supporting the development and function of normal osteoclasts in this mutation. 相似文献
4.
Thus, we can conclude that marrow transplantation has already influenced medical practice greatly. It has offered a treatment which often cures patients of more than 20 otherwise lethal diseases. The treatment so horrendously difficult and dangerous at first has already been greatly improved, simplified, and made much safer. The availability of a suitable donor has been much extended and real progress has been made in prevention and perhaps even in treatment of graft-versus-host disease. This has made possible the option of marrow transplantation for every patient in whom we think the treatment may be beneficial. The problem underlying many cases of interstitial pneumonia has been identified and patients are already benefitting clinically from this progress. Progress has also been made which promises antiviral therapy which could reduce, prevent, and ultimately eliminate the intercurrent virus infections which limit the applicability of marrow transplantation, especially for children with severe immunodeficiencies. I do not know how far this line of investigation can be taken. However, just as we have learned stepwise to use marrow transplants from matched siblings to treat many diseases, to use fetal liver in place of bone marrow, to employ matched relative donors when a matched sibling is not available, and, finally, even to use parental donors to achieve correction of SCID, we now have good reason to believe that, ultimately, we can use marrow transplantation without fear of GVHD to address many additional genetically determined and acquired diseases; certainly, for those diseases that involve any of the cells that are derived from bone marrow cells, and perhaps for those attributable even to cells of other organs and tissues, the functions of which are, in whole or in part, a consequence of interactions of marrow-derived cells and cells of ectodermal or endodermal origin, marrow transplantation may be useful. To us, the future of marrow transplantation as a major modality of treatment or prevention of many diseases, including hemoglobinopathesis, immunodeficiencies, hematologic abnormalities, abnormalities of function of marrow-derived cells, and even inborn errors of function of cells of organs and tissues not of marrow origin, seems bright, indeed. Further, with the capacity to introduce resistance genes against viruses and malignancies, autoimmune diseases, and diseases dependent on anomalies of immune response genes, marrow transplantation for many other diseases seems a more remote possibility.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
5.
Westminster experience had by 1973 evolved the concept of displacement bone marrow transplantation and extended the donors from matched siblings to other family and unrelated donors. The principles of its use to install donor bone marrow as a component factory for the life of the recipient, together with the importance of immunoprophylaxis are detailed. Satisfying correction has been achieved for 48 previously fatal genetic diseases, partial correction for another 5 with failure for 3 diseases. Displacement bone marrow transplantation is not a panacea, but could be applied to about 7% of known inborn errors, devising in vitro tests which can predict in vivo donor effects, especially since some 80% of our patients are not found in known families and could not have been prevented. 相似文献
6.
异基因造血干细胞移植(allo-HSCT)是治愈多种非恶性病的有效方法。脐带血干细胞(UCB)具有免疫原性低、人类白细胞抗原不合耐受性好、移植物抗宿主反应发生率低以及获取相对快捷等特点,可作为非恶性血液疾病患者allo-HSCT的来源。本文简要综述脐血干细胞移植在原发性免疫缺陷病、遗传性骨髓衰竭、遗传代谢病以及自身免疫性疾病等非恶性血液疾病的治疗效果。 相似文献
7.
胚胎发育中,肝脏是一个重要的造血器官。近年来胎肝移植的临床应用重新引起了人们的关注。本文应用染色体的 C-带染色法研究了小鼠骨髓和胎肝造血干细胞在照射受体小鼠中的增殖能力与相互间的竞争作用。实验结果表明胎肝造血干细胞在成年骨髓中的植入率比较同样条件下的成年骨髓造血干细胞低,但胎肝造血干细胞比较成年骨髓造血干细胞具有更强的自我更新或增殖能力。在同种胎肝造血干细胞移植中,为了降低同种移植抗力,提高移植的胎肝造血干细胞在受体中的耐受性,移植前对受体作适当的免疫抑制处理是必要的。因此,克服个体发育屏障和移植免疫屏障是提高同种胎肝造血干细胞移植效果中两个重要的研究课题。 相似文献
8.
In utero bone marrow transplantation to fetuses offers the potential advantage of ameliorating the effects of genetic disorders by transplanting allogeneic hematopoietic stem cells into recipients who are immunoincompetent and require no preparative regimen. Therefore, we undertook studies to examine the feasibility of in utero bone marrow transplantation of unrelated allogeneic adult bone marrow into fetal baboons. Thirty-one baboon fetuses were transplanted between the ages of 60 and 160 days gestation (normal gestation, 182 days) with unrelated allogeneic adult bone marrow containing a different isozyme of glucose-phosphate isomerase (GPI). Approximately one third of the 80-day fetuses demonstrated engraftment 1 month after transplantation. Three of three of the initial chimeras died in utero 45 to 80 days after transplantation and the remaining chimeras lost their graft. Furthermore, 80-day fetal baboons were able to recognize donor cells, maternal cells, and other adult baboon peripheral blood cells in a mixed lymphocyte culture (MLC) reaction but still could engraft with allogeneic bone marrow. In contrast all nonchimeric animals survived to term. These data suggest that fetal transplantation of primates is feasible using techniques employed in these studies and that transplantation of younger fetuses who are immunocompetent should be attempted. 相似文献
9.
Shields LE Gaur L Delio P Gough M Potter J Sieverkropp A Andrews RG 《Journal of medical primatology》2005,34(4):201-208
In utero hematopoietic stem cell transplantation is a therapeutic procedure that could potentially cure many developmental diseases affecting the immune and hematopoietic systems. In most clinical and experimental settings of fetal hematopoietic transplantation the level of donor cell engraftment has been low, suggesting that even in the fetus there are significant barriers to donor cell engraftment. In postnatal hematopoietic transplantation donor cells obtained from mobilized peripheral blood engraft more rapidly than cells derived from marrow. We tested the hypothesis that use of donor hematopoietic/stem cells obtained from mobilized peripheral blood would improve engraftment and the level of chimerism after in utero transplantation in non-human primates. Despite the potential competitive advantage from the use of CD 34(+) from mobilized peripheral blood, the level of chimerism was not appreciably different from a group of animals receiving marrow-derived CD 34(+) donor cells. Based on these results, it is unlikely that this single change in cell source will influence the clinical outcome of fetal hematopoietic transplantation. 相似文献
10.
O. V. Payushina N. N. Butorina O. N. Sheveleva S. S. Bukhinnik A. A. Berezina S. G. Ramazanova E. I. Domaratskaya 《Russian Journal of Developmental Biology》2017,48(4):269-277
The aim of this study was to analyze the changes that occur in the population of bone marrow mesenchymal stromal cells (MSCs) during the individual development of an organism. For this purpose, the basic characteristics of MSCs (the content of clonogenic cells, immunophenotype, and potencies to differentiate in vitro and in vivo) in the prenatal, early postnatal, and late postnatal ontogeny of the rat were compared. It is shown that the cloning efficiency of bone marrow MSCs in 10-day-old and adult rats is comparable and hundreds of times smaller than that of bone cells of 20-day-old fetuses with a bone marrow rudiment. The activity of alkaline phosphatase, a marker of osteogenic cells, was found in the majority of colonies formed by MSCs of postnatal bone marrow but not by the fetal bone. By the CD90 expression and potencies for in vitro adipogenesis, the stromal cells from the fetal bone and bone marrow of 9- to 10-day-old rats were comparable with those of the mature bone marrow MSCs but differed from them by the small number of CD73-bearing cells and a weaker ability to osteogenesis in an inductive environment. The analysis of the fate of MSCs from the studied sources after their transplantation to adult rats showed that their ectopic transplantation as part of tissue fragments into the kidney results in the formation of bone tissues and hematopoietic stroma. In diffusion chambers with MSCs that were precultured in vitro, transplantation into the peritoneal cavity led to osteogenesis and chondrogenesis. However, no significant differences in the potencies of bone marrow MSCs for differentiation in vivo depending on the developmental stage have been found. Thus, during ontogeny, bone marrow MSCs enhance the expression of CD73 and the ability to osteogenesis in vitro, whereas the expression of CD90 and the potencies for adipogenesis in induction medium and differentiation in different directions in vivo do not change significantly. 相似文献
11.
经体内扩散盒培养6d 后的 LACA 小鼠胎肝细胞移植给照射的同系成年小鼠,造血干细胞在受体脾脏和骨髓中的有效植入率比正常胎肝细胞明显提高。但这种效果在同种异基因受体小鼠中则完全消失。实验结果表明,个体发育屏障和移植免疫屏障是决定同种胎肝移植能否成功的两个重要因素。胎肝细胞经体内或体外培养后可以模拟造血干细胞在体内的发育成熟,从而增强对成年造血微环境的适应性。用短期体内培养的方法,可以改变胎肝造血干细胞的某些生理特性,从而减弱个体发育屏障,但不能克服胎肝同种移植中的免疫性抗力。为了保证同种胎肝移植的成功,必须进一步同时克服两种屏障。 相似文献
12.
肝硬化是一种临床常见的肝病良性终末期表现。目前临床上尚缺乏有效的治疗措施。肝脏移植是最理想的治疗方法,但受供体肝脏来源限制,且费用昂贵。近年来开展的自体骨髓干细胞(BMSCs)移植治疗,为肝硬化的治疗带来了新的希望。BMSCs主要包括造型血干细胞和间充质干细胞,其具有可塑性,体外通过生长因子,体内利用特定微环境均可诱导BMSCs分化为肝前体细胞和成熟肝细胞,并明显改善肝功能。从动物实验到临床研究亦表明,BMSCs具有来源丰富、费用低廉、损伤小、自体移植不栓塞、无排斥反应等优点,为治疗肝病带来了新思路,有望成为生物人工肝的细胞来源。本文就BMSCs移植治疗肝硬化的研究现状,尤其是移植途径以及在肝脏内定居、迁移和分化机制的示踪观察方法和存在的问题作一综述,以期为从事肝病研究的同仁提供参考依据。通过对BMSCs移植从基础研究及临床应用的最新进展的描述,展示BMSCs在肝硬化治疗方面良好的治疗前景。 相似文献
13.
Current status of bone marrow transplantation in humans: report from the International Bone Marrow Transplant Registry 总被引:3,自引:0,他引:3
Bone marrow transplantation is being used with increasing frequency as therapy for a number of life-threatening diseases. Data reported to the International Bone Marrow Transplant Registry are presented to show the pattern of growth of bone marrow transplantation worldwide as well as current results in leukemia and aplastic anemia. Risk factors are identified that may predict the development of major complications after bone marrow transplantation. 相似文献
14.
Alpha-smooth muscle actin is expressed in a subset of bone marrow stromal cells in normal and pathological conditions 总被引:1,自引:0,他引:1
A Schmitt-Gr?ff O Skalli G Gabbiani 《Virchows Archiv. B, Cell pathology including molecular pathology》1989,57(5):291-302
A series of 217 trephine bone marrow biopsies from adult patients and specimens from 16 fetuses and 5 infants were examined for the presence of stromal myoid cells (MCs) using a monoclonal antibody recognizing alpha-smooth muscle actin. In the normal adult bone marrow, stromal cells did not contain alpha-smooth muscle actin, whereas during fetal life, many alpha-smooth muscle actin-containing MCs were connected with vascular sinusoids in the primitive bone marrow. This cell type reappeared in various characteristic distribution patterns in adult bone marrow during different neoplastic and non-neoplastic conditions including metastatic carcinoma, Hodgkin's disease, multiple myeloma, hairy cell leukemia, acute myeloid leukemia (FAB M4, 5, 7) and chronic myelo-proliferative diseases. In general, the appearance of MCs was associated with a slight to pronounced increase in the deposition of reticulin and collagen fibers. We propose that bone marrow MCs represent a distinct subpopulation of fiber-associated or adventitial reticular cells undergoing cytoskeletal remodeling in response to various stimuli. 相似文献
15.
同种异体宫内移植小鼠嵌合模型的建立 总被引:1,自引:0,他引:1
干细胞宫内移植是一种很有前途的产前治疗方式。为深入研究干细胞移植后的细胞行为,采用宫内移植的方法建立同种异体的嵌合小鼠模型。将雄鼠骨髓单核细胞宫内注射到胎鼠腹腔,在受体鼠出生后检测雌性受体鼠外周血细胞。应用PCR检测外周血是否存在雄性鼠的DNA,并采用定量PCR技术确定其嵌合量;同时用荧光原位杂交(FISH)技术直观观察外周血中雄性来源的细胞。结果表明:共获得4只阳性外周血嵌合小鼠,其中3只稳定嵌合达到6个月以上。应用宫内移植成功建立了外周血中存在异源细胞的小鼠嵌合模型。 相似文献
16.
Mesenchymal stem cells (MSCs) can be derived from adult bone marrow, fat and several foetal tissues. In vitro , MSCs have the capacity to differentiate into multiple mesodermal and non-mesodermal cell lineages. Besides, MSCs possess immunosuppressive effects by modulating the immune function of the major cell populations involved in alloantigen recognition and elimination. The intriguing biology of MSCs makes them strong candidates for cell-based therapy against various human diseases. Type 1 diabetes is caused by a cell-mediated autoimmune destruction of pancreatic β-cells. While insulin replacement remains the cornerstone treatment for type 1 diabetes, the transplantation of pancreatic islets of Langerhans provides a cure for this disorder. And yet, islet transplantation is limited by the lack of donor pancreas. Generation of insulin-producing cells (IPCs) from MSCs represents an attractive alternative. On the one hand, MSCs from pancreas, bone marrow, adipose tissue, umbilical cord blood and cord tissue have the potential to differentiate into IPCs by genetic modification and/or defined culture conditions In vitro . On the other hand, MSCs are able to serve as a cellular vehicle for the expression of human insulin gene. Moreover, protein transduction technology could offer a novel approach for generating IPCs from stem cells including MSCs. In this review, we first summarize the current knowledge on the biological characterization of MSCs. Next, we consider MSCs as surrogate β-cell source for islet transplantation, and present some basic requirements for these replacement cells. Finally, MSCs-mediated therapeutic neovascularization in type 1 diabetes is discussed. 相似文献
17.
Major progress in experimental and clinical research has made allogeneic bone marrow transplantation a highly effective therapy for a variety of malignant and nonmalignant diseases. Allogeneic bone marrow transplantation from histocompatible donors is now the therapy of choice for some of these disorders. We review in part I the history, technical approach, complications, and the results achievable with this therapeutic approach. Further experimentation and future goals are also discussed. 相似文献
18.
Annette Schmitt-Gräff Omar Skalli Giulio Gabbiani 《Virchows Archiv. B, Cell pathology including molecular pathology》1989,57(1):291-302
A series of 217 trephine bone marrow biopsies from adult patients and specimens from 16 fetuses and 5 infants were examined
for the presence of stromal myoid cells (MCs) using a monoclonal antibody recognizing α-smooth muscle actin. In the normal
adult bone marrow, stromal cells did not contain α-smooth muscle actin, whereas during fetal life, many α-smooth muscle actin-containing
MCs were connected with vascular sinusoids in the primitive bone marrow. This cell type reappeared in various characteristic
distribution patterns in adult bone marrow during different neoplastic and non-neoplastic conditions including metastatic
carcinoma, Hodgkin’s disease, multiple myeloma, hairy cell leukemia, acute myeloid leukemia (FAB M4, 5, 7) and chronic myeloproliferative
diseases. In general, the appearance of MCs was associated with a slight to pronounced increase in the deposition of reticulin
and collagen fibers. We propose that bone marrow MCs represent a distinct subpopulation of fiber-associated or adventitial
reticular cells undergoing cytoskeletal remodeling in response to various stimuli. 相似文献
19.
Yuka Tanaka Tomoko Inoue-Yokoo Kasem Kulkeaw Chiyo Yanagi-Mizuochi Senji Shirasawa Yoichi Nakanishi Daisuke Sugiyama 《PloS one》2015,10(9)
In mice, hematopoietic cells home to bone marrow from fetal liver prenatally. To elucidate mechanisms underlying homing, we performed immunohistochemistry with the hematopoietic cell marker c-Kit, and observed c-Kit(+) cells localized inside muscle surrounding bone after 14.5 days post coitum. Flow cytometric analysis showed that CD45(+) c-Kit(+) hematopoietic cells were more abundant in muscle than in bone marrow between 14.5 and 17.5 days post coitum, peaking at 16.5 days post coitum. CD45(+) c-Kit(+) cells in muscle at 16.5 days post coitum exhibited higher expression of Gata2, among several hematopoietic genes, than did fetal liver or bone marrow cells. Colony formation assays revealed that muscle hematopoietic cells possess hematopoietic progenitor activity. Furthermore, exo utero transplantation revealed that fetal liver hematopoietic progenitor cells home to muscle and then to BM. Our findings demonstrate that hematopoietic progenitor cell homing occurs earlier than previously reported and that hematopoietic progenitor cells reside in muscle tissue before bone marrow hematopoiesis occurs during mouse embryogenesis. 相似文献
20.
目的研究制备人鼠肝组织嵌合小鼠模型。方法将人骨髓干细胞直接注射到一定日龄胎鼠肝组织,每只注射移植约1×109人骨髓干细胞。用免疫组化对出生一定日龄移植小鼠肝脏进行甲胎蛋白免疫组织化学检测,检定分析人肝细胞在小鼠体内嵌合生长情况。结果移植人骨髓干细胞胎鼠出生2月龄、12月龄可检测到甲胎蛋白。结论将人骨髓干细胞移植小鼠肝脏内能够存活并分化成人肝细胞并能够长期存活。 相似文献