The article reviews concisely around the history of hematopoietic stem cell research, basic and clinical, since its very beginning after the nuclear explosions at the end of the Second World War, that explains why the stem cell study in the world began with the hematopoietic stem cells and the existence of non-hematopoietic stem cell in vivo had been left out of account for many decades till 21st century. During 50-60s of the last century, it was known from the animal experiments that there must be hematopoietic stem cells existing in vivo and believed that the effective bone marrow transplant is actually the stem cell transplantation. It is reviewed how the basic studies of stem cell interacted with the clinical stem cell transplantation and how great the contribution was given to strongly push forward the development of contemporary stem cell biology and modern hematology from the basic studies especially in the immunological and molecular biological fields, for instance, the applications of HLA technology and monoclonal antibody produced, flow cytometry, and genetic recombinant cytokines, the novel technique for gene cloning, genomics, proteomics, and iRNA as well as bioinformatics. It has lead to the pluralistic cell therapy as a novel trend in stem cell transplantation as to combine immunotherapy and mesenchymal stem cells with the conventional stem cell transplants. This paper looks back in the past several decades, however, on every achievement of stem cell study that were usually accompanied with some idealistic one-sidedness or even errors in design and conclusion of some experiments. Usually it took a period of 2 or even 4 decades to clarify some basic idea, that seemed normal in the science development, for examples, the dividing line between the hematopoietic stem cell and progenitor cells, possibility to expand or clone the real stem cell ex vivo, and whether the majority of leukemias are originated from stem cell level, etc. Towards the end of 20th century, the greatest discovery was the existence of adult stem cells in adult tissues, which are no doubt the remnants from the embryonic development including all stages of embryonic stem cells, very earlier and later, hematopoietic and nonhematopoietic, and could be induced to differentiate into all kinds of tissue cells by proper ways in vitro. No evidence has really provided for the hypothesis of so called trans-differentiation or de-differentiation, which brought about strong calls in questions in the past 5 years. The problems in developing the clinical gene therapy by using hematopoietic stem cell as carrier of interested gene still remained to be solved so far. Because of the relatively weak base of related basic studies, the clinical application of gene therapy resulted in the failure of clinical practice with lots of lessons towards the end of last century. The whole history of stem cell study in the world was an endless process of continuous redress for theoretical ideas in stem cell biology that had never been consummate.
Hematopoietic Stem Cells ; cytology ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Research ; history ; standards ; Research Design ; standards

More works documented recently indicated that human CD34(-) cells exist and are likely to be the precursors of the CD34(+) cells. Anyhow, the CD34(+) enriched populations have already been proved to show long-term reconstitution of hematopoiesis in animals and patients worldwidely. It still remains uncertain whether cells lack of CD34 and Lineage markers are the very best stem cells or maybe the residual embryonic stem cells keeping quiescent in the adult tissues are capable of transfer into hematopoietic stem cells when activated. Since just a negative selection technique is used to collect the CD34(-) cells everywhere for the time being, no final conclusion is convincing about the characterization of CD34(-) cells till a highly purified cell population of CD34(-)/Lin(-) is available. Clinical analysis shows that the most critical factor predicting the stem cell engraftment is the number of the cells infused. The number of nucleated cells in umbilical cord blood to be infused and required to obtain a successful engraftment is superior to 3.7 x 10(7)/kg. However, large dose of T-cell-depleted and purified CD34(+) cells as more than 5 x 10(6)/kg or even a 'megadose' of CD34(+) cells of 10(7)/kg is recommended for allotransplant of mobilized peripheral blood to achieve a high rate of successful engraftment. The delayed engraftment and the relapse of malignancy after cord blood transplantation are major problems. However, CBT is still the best choice of stem cell transplant for the baby patients with non-malignancies. At present, the HLA typing for class I antigens is still achieved with serology in most laboratories. As HLA typing is increasingly defined to higher degree of resolution by DNA probes, it is recommended to check with genotyping when there is a 'match' by the serological phenotyping especially for the unrelated donor/recipient couples. Improvements in DNA-based methods for the detection of numerous HLA alleles have provided the opportunity to investigate the relationship between HLA disparity and transplant complications. About 80% (or even more) of patients in China who might benefit from stem cell transplantation still fail to find suitable donors. It is worthy to adopt the unrelated donors matched or mismatched for those high-risk acute leukemia patients who do not have related matched donors but urgently need transplant. The advanced experience of unrelated mismatched transplant will no doubt be certain to carry weight and be disseminated in China. A great leap forward of the clinical practice and biological study on hematopoietic stem/progenitor cells is expected in the new century to accept the challenge from the world outside China.

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective and proven treatment for malignant and nonmalignant diseases. Most of the natural HSC allografts hardly show overall advantages of high engraftment, slight GVHD and rare relapse. The graft engineering including stem cell engineering to make a tailor-made graft ex vivo is promising to conquer all the risks of low engraftment, lethal GVHD and high relapse, which becomes the key program in current HSC research. To combine HSC allotransplant with gene therapy and immune therapy is the novel therapeutic strategy for malignancies, the real meaning of "cytotherapy" or "cell therapy" updated. The rapid expansion of umbilical cord blood banks (CBBs) makes the substantial increase of cord blood transplants (CBT) both possible and likely world-widely. In China, however, owing to lack of hematological pediatricians specified in HSCT and pediatric laminar-flow wards, clinical application rate of cord blood is extremely low despite of the high collection rate in the CBBs under the GMP standards. In evaluating a CBB, the release rate and the clinical efficacy of the released cord blood should be most emphasized as well as the banking quality control. In all CBBs worldwide, it is unworthy of mentioning the banking of umbilical cord blood for autologous transplant. Only one or two commercial companies in the world run it for profitable purpose to charge the donor parents regularly. It is because no autologous CBT can cure the inherited diseases and its efficacy of treating malignancies is doubtable since the cord blood is of weak immune competence against tumor and may be contaminated with autologous malignant or premalignant cells. Moreover, there is no report so far about how long the repopulating activity of cryopreserved hematopoietic stem/progenitor cells of cord blood can keep. No honest guarantee can be made about the effective quality and adequate amount of stem cells to meet the therapeutic requirement when used after a long storage.

The basic studies selected were mainly published since 1998 and related to stem cell biology and engineering and particularly the efforts for developing new sources of hematopoietic stem/progenitor cells ex vivo. Hematopoietic cells and lymphocytes can be developed by induced differentiation in a appropriate way of culture, originating in the embryo- or adult-derived stem cells or tissue-committed stem cells which still exist in the tissue of adults. The most primitive multipotential embryonic stem cell from embryo or adult tissue has the plasticity to differentiate into every kind of progenies, the committed tissue-specific stem cell, by different proper ways of induction in vitro. The committed tissue-specific stem cell, however, can only be induced to differentiate along the line of its committed origin of tissue. No studies in China strongly confirmed yet the existence of "transdifferentiation" among the tissue- or organ-specific stem cells.
Adult ; Cell Differentiation ; Cell Lineage ; China ; Embryo, Mammalian ; cytology ; Hematopoietic Stem Cells ; cytology ; Humans ; Mesoderm ; cytology ; Models, Biological ; Pluripotent Stem Cells ; cytology ; Research ; trends ; Stem Cells ; cytology

Clavicle ; injuries ; surgery ; Fracture Fixation, Internal ; methods ; Fractures, Bone ; surgery ; Humans

Adult ; China ; Humans ; Mesenchymal Stem Cell Transplantation ; Research

The mechanism of drug resistance about ATRA curing acute promyelocytic leukemia involves many aspects and was not understood completely now. Among them, gene, protein and cell signal conduction way have become hot points that scientists are focusing on recently.

Gastrectomy ; methods ; Humans ; Laparoscopy ; Stomach Neoplasms ; surgery

Humans ; Lymphoma, Large-Cell, Anaplastic ; diagnosis ; enzymology ; therapy ; Receptor Protein-Tyrosine Kinases

Objective To explore the relationship between diethylhexylphthalate (DEHP) and peritoneal sclerosis and its possible mechanism. Methods Isolated human peritoneal mesothelial cells (HPMC) was cultured for five days in culture solution with varied doses of DEHP ７．７?of 10-6mol/L (A group), 5.4?１０－５mol/L (B group) and 2. 2?10-4 mol/L (C group) respectively. Culture solution without DEHP was as control. Total collagen synthesis and secretion was assayed by 3H-proline incorporation. ELISA method was used to detect the level of secreted fibronectin (FN) . The expression of FN mRNA , collagen ImRNA, collagen Ⅲ mRNA and TGF－?l mRNA was determined by RT-PCR. Results (1)HPMC expressed FN, laminin, collagen Ⅲ and TGF-?１. (2)DEHP stimulated FN and collagen expression with a higher level in C group compared with control(P