Breast cancer micrometastases: Different interactions of carcinoma cells with normal and cancer patients' bone marrow stromata

The apparently dormant breast cancer micrometastases in haemopoietic marrow are correlated with distant metastatic carcinoma dissemination. We studied in vitro interactions of carcinoma cells with adjacent stromata, using connective tissue cell cultures from breast and bone marrow samples of normal donors, comparing them to the pericancerous breast tissue and bone marrows of 12 selected patients with invasive breast carcinomas. Cancer cells were detected by immunocytochemistry and RT-PCR in all the bone marrows and in most blood samples of the studied patients. We monitored the growth and interaction of carcinoma MCF-7 cells with the stromata. The normal breast stroma sustained typical massive cancer growth. The pericancerous breast stroma induced the invasive mesenchymal pattern of growth. Normal bone marrow stroma induced the same conversion and was highly adhesive, retaining the cells in the stroma, but carcinoma patients' bone marrow stromata underwent low adhesive interactions with cancer cells, releasing them potentially into the circulation. The semi-quantitative RT-PCR indicated an enhanced expression of the hepatocyte growth factor and its receptor c-met in breast and bone marrow stromata of cancer patients. The input of cancer cells into the normal bone marrow may induce modifications of the local microenvironment, favourable for growth and release of carcinoma cells into the systemic circulation, which correlate with the poor prognosis of patients with bone marrow micrometastases. This revised version was published online in July 2006 with corrections to the Cover Date.     

The expression of neurokinin-1 and preprotachykinin-1 in breast cancer cells depends on the relative degree of invasive and metastatic potential

Breast cancer has a predilection for metastasis to the bone marrow. The preprotachykinin-I (PPT-I) gene has a central role in the early migration of breast cancer cells into the bone marrow, making this organ a latent repository of the cancer cells. This study investigated whether the invasive and metastatic potential of breast cancer cells correlate with the expression of the PPT-I gene and the receptors for its peptides, neurokinin-1 (NK-1) and NK-2. The studies compared cells that are non-tumorigenic (MCF12A), low metastatic and invasive potential (MCF7), and sublines of MCF with increased invasive and metastatic potential (LCC1 and LCC2). LCC2, but not LCC1 is tamoxifen resistant. Quantitative RT-PCR showed increased expression of PPT-I, NK-1 and NK-2 mRNA LCC1 and LCC2. MCF7 required stimulation by phorbol ester for NK-1 induction. The levels of NK-2 mRNA were significantly increased in LCC2. Clonogenic assays with specific receptor antagonists showed a predominant role for NK-2 in the proliferation of both LCC1 and LCC2. While the growth rate of LCC1 and LCC2 were similar, the latter showed increased migration. Use of a nude mouse model confirmed higher metastatic potential of LCC2, including increased migration to regions of the endosteum. Overall, these studies show a correlation between three neuroendocrine-related genes: PPT-I, NK-1 and NK-2 and the metastatic potential of specific breast cancer cells. These cells provide a model for future studies on bone marrow metastasis.This work was done at UMDNJ-New Jersey Medical School, Departments of Pathology and Laboratory Medicine and Medicine-Hematology/Oncology.     

Chemokine receptor CXCR4 expression in breast cancer as a potential predictive marker of isolated tumor cells in bone marrow

Interactions between the CXCR4 chemokine receptor in breast cancer cells and the ligand CXCL12/SDF-1α are thought to play an important role in breast cancer metastases. In this pilot study, CXCR4 expression along with other biomarkers including HER2-neu and EGFR, were measured in primary tumor samples of patients with operable breast cancer to test whether any of these biomarkers alone and in combination could indicate breast cancer with high likelihood of metastasizing to bone marrow. Cytokeratin (CK) positive cells in bone marrow were identified by flow-cytometry following enrichment with CK 7/8 antibody-coupled magnetic beads. Primary tumors (n = 18) were stained with specific antibodies for CXCR4, HER2-neu, EGFR, and PCNA using an indirect avidin–biotin horseradish peroxidase method. The majority of the patients had T2/T3 tumors (72%), or lymph node involvement (67%) as pathologic characteristics that were more indicative of high-risk breast cancer. High CXCR4 cytoplasmic expression was found in 7 of 18 patients (39%), whereas 6 of 18 patients (33%) were found to have CK positivity in bone marrow. The median number of CK⁺ cells was 236 (range, 20–847) per 5 × 10⁴ enriched BM cells. The presence of CK⁺ cells in bone marrow was found to be associated with increased expression of CXCR4 alone or in addition to EGFR and/or HER2-neu expression (P = 0.013, P = 0.005, and P = 0.025, respectively) in primary tumors. Furthermore, three patients with high CK positivity (>236 CK⁺ per 5 × 10⁴ enriched bone marrow cells) in bone marrow exclusively expressed high levels of CXCR4 with EGFR/HER2-neu (P = 0.001). Our data suggest that high CXCR4 expression in breast cancer may be a potential marker in predicting isolated tumor cells in bone marrow. CXCR4 coexpression with EGFR/HER2-neu might further predict a particular subset of patients with high CK positivity in bone marrow.     

Differential expression of osteopontin and bone sialoprotein in bone metastasis of breast and prostate carcinoma

Breast and prostate cancer often metastasise to the skeleton. Interestingly, the histopathological characteristics of the bone lesions that arise from these two cancer types differ. Breast tumours give rise to metastases in the skeleton with a mixed lytic/sclerotic pattern, whereas a predominantly sclerotic pattern is seen in metastases from prostate tumours. Osteopontin (OPN) and bone sialoprotein (BSP) are bone matrix proteins that have been implicated in the selective affinity of cancer cells for bone. In the present study, 21 patient cases with skeletal metastasis and their respective primary tumours (12 with breast cancer, 9 with prostate cancer) were investigated by immunohistochemistry in order to assess the level of OPN and BSP. Moderate to strong OPN expression was found in 42% of all breast tumours and in 56% of all prostate tumours. Significantly more breast cancer bone metastases exhibited high OPN expression, 83%, as compared with prostate tumour bone metastases, 11% (P=0.0019). In contrast, moderate to strong BSP expression was found in 33% of breast tumours and in 89% of prostate tumours. In the bone lesions, only 33% of breast tumour metastases showed moderate/strong BSP expression compared to 100% of prostate tumour metastases (P=0.0046). This divergent pattern of OPN/BSP expression could be an important determinant for the different characteristics of these two types of bone metastasis, i.e., lytic vs. sclerotic, consistent with the proposed role of OPN in differentiation and activation of osteoclasts and of BSP as a stimulator of bone mineralisation. This revised version was published online in July 2006 with corrections to the Cover Date.     

Localization of osteoblast inflammatory cytokines MCP-1 and VEGF to the matrix of the trabecula of the femur,a target area for metastatic breast cancer cell colonization

Bone likely provides a hospitable environment for cancer cells as suggested by their preferential localization to the skeleton. Previous work has shown that osteoblast-derived cytokines increased in the presence of metastatic breast cancer cells. Thus, we hypothesized that osteoblast-derived cytokines, in particular IL-6, MCP-1, and VEGF, would be localized to the bone metaphyses, an area to which breast cancer cells preferentially traffic. Human metastatic MDA-MB-231 breast cancer cells were inoculated into the left ventricle of the heart of athymic mice. Three to four weeks later, tumor localization within isolated femurs was examined using μCT and MRI. In addition, IL-6, MCP-1, and VEGF localization were assayed via immunohistochemistry. We found that MDA-MB-231 cells colonized trabecular bone, the area in which murine MCP-1 and VEGF were visualized in the bone matrix. In contrast, IL-6 was expressed by murine cells throughout the bone marrow. MDA-MB-231 cells produced VEGF, whose expression was not only associated with the breast cancer cells, but also increased with tumor growth. This is the first study to localize MCP-1, VEGF, and IL-6 in bone compartments via immunohistochemistry. These data suggest that metastatic cancer cells may co-opt bone cells into creating a niche facilitating cancer cell colonization.     

Bone marrow cells engraft within the epidermis and proliferate in vivo with no evidence of cell fusion

In adults, bone marrow-derived cells (BMDC) can contribute to the structure of various non-haematopoietic tissues, including skin. However, the physiological importance of these cells is unclear. This study establishes that bone marrow-derived epidermal cells are proliferative and, moreover, demonstrates for the first time that BMDC can localize to a known stem cell niche: the CD34-positive bulge region of mouse hair follicles. In addition, engraftment of bone marrow cells into the epidermis is significantly increased in wounded skin, bone marrow-derived keratinocytes can form colonies in the regenerating epidermis in vivo, and the colony-forming capacity of these cells can be recapitulated in vitro. In some tissues this apparent plasticity is attributed to differentiation, and in others to cell fusion. Evidence is also provided that bone marrow cells form epidermal keratinocytes without undergoing cell fusion. These data suggest a functional role for bone marrow cells in epidermal regeneration, entering known epidermal stem cell niches without heterokaryon formation.     

A murine model for bone marrow metastasis established by an i.v. injection of C-1300 neuroblastoma in A/J mice

A reproducible tumor model for bone marrow metastasis has been developed by an injection of murine C-1300 neuroblastoma (C-1300 NB) cells into the tail vein of syngeneic A/J mice. The animals died with liver metastases at 18–21 days after an injection of 10⁵ tumor cells and often had bone marrow metastasis in the femur. N-methylformamide (NMF), a maturational agent, was administered to inhibit liver metastases and to extend survival in mice with advancing bone metastasis. Histological examination of bone marrow metastasis, demonstrated lesions varying from a few small colonies of C-1300 NB cells either in metaphysis or diaphysis to large foci replacing normal hematopoietic bone marrow, simultaneously invading epiphysis or cortex of bone as bone metastasis. This assay demonstrated the ability to detect neuroblastoma cells in the bone marrow histologically and could determine bone marrow TD₅₀ by extraction of bone marrow cells after treatment with various doses of drug. Fifty per cent of mice injected with cyclophosphamide (CY) developed bone marrow metastasis without liver metastasis. Treatment with tamoxifen, an anti-calmodulin drug, suppressed tumor takes in the recipient mice with tamoxifen-dose-dependent fashion. This experimental system allows for investigations into the therapeutic response and biology of neuroblastoma metastases in the bone marrow.     

Prominent gelatinous bone marrow transformation presenting prior to myelodysplastic syndrome: a case report with review of the literature

Gelatinous bone marrow transformation (GMT) is a rare disorder characterized by the presence of fat cell atrophy, loss of hematopoietic cells, and deposition of extracellular gelatinous materials. GMT is not a specific disease, but is strongly associated with malnutrition and drugs. Albeit extremely rare, GMT has been reported in patients with myeloproliferative disorders. Herein, we report the second documented case of hypoplastic myelodysplastic syndrome (MDS) accompanying GMT. A 73-year-old Japanese male with excellent nutrition status and no history of alcohol or drug intake was detected with pancytopenia. The initial bone marrow aspirate specimen reveled hypocellular marrow without dysplastic signs in the myeloid cells. Bone marrow biopsy demonstrated hypocellular bone marrow with prominent GMT. He received blood transfusions, however, pancytopenia continued to progress. The second bone marrow aspirate specimen showed dysplastic changes, such as pseudo-Pelger-Huët cells, hypogranular or agranular granulocytes, and megakaryocytes with multiple small nuclei. Cytogenetic study demonstrated deletion of chromosome 7. Therefore, an ultimate diagnosis of hypoplastic MDS accompanying GMT was made. Only a limited number of cases of myeloproliferative disorders with GMT have been reported. Our analysis of these cases revealed that chromosome 7 abnormality is frequently observed in this condition. Moreover, findings from the current case suggested that myeloproliferative disorders including MDS must be included in the differential diagnostic considerations of GMT patients, who have no history of malnutrition or drugs, and careful examination of the bone marrow smear specimen and cytogenetic analysis are necessary for early detection of underlying myeloproliferative disorders.     

自体骨髓细胞移植和心肌血管新生

治疗性血管生成是治疗缺血性心脏病的新方法,而自体骨髓细胞移植为血管生治疗开辟了新的途径并受到广泛的关注.本文结合最近几年内的相关研究,对于骨髓细胞移植与促血管生成的有关细胞学基础、相关机制作了分析,同时对于骨髓细胞移植用于促心肌血管生成治疗的有关动物和临床实验作了回顾和评价.     

Regression of bone metastases following adoptive transfer of anti-CD3-activated and IL-2-expanded tumor vaccine draining lymph node cells

As many as 80% of patients with breast, prostate, or lung cancer develop bone metastases during the course of their illness. However, thus far, no attempts have been made to explore the potential value of adoptive immunotherapy with antigen-specific T lymphocytes specifically for the treatment of skeletal metastases. Here, we demonstrate tumor regression in a preclinical model of bone metastases from the murine B16BL6 melanoma following adoptive transfer of effector T lymphocytes obtained from tumor vaccine draining lymph nodes. The antitumor effect required transfer of high number of effector cells, which was dependent on CD8+ cells as demonstrated by in vivo depletion of different T cell subsets, and was magnified if effector cells were administered to the arterial supply of the bone/bone marrow. Using flow cytometric analysis, CFSE-labelled Thy1.1+ donor T cells were isolated from the bone marrow of tumor-bearing mice at 24 h and 6 days following adoptive transfer. At the latter time point cell division of the transferred effector cells was detectable. Currently, no curative treatment is known for skeletal metastases in clinical practice. Considering the promising early findings in the present study, further studies exploring the therapeutic potential of adoptive immunotherapy for metastatic disease to the skeleton are warranted.     

Long-Term Culture of Human Bone Marrow Stromal Cells in the Presence of Basic Fibroblast Growth Factor

Abstract

Basic fibroblast growth factor (bFGF) is a potent mitogen for human bone marrow stromal cells. Normally, large numbers of human bone marrow stromal cells are difficult to obtain. However, nanogram/ml concentrations of bFGF stimulate the growth of passaged bone marrow stromal cells both in media formulated for optimal growth of stromal cells and in a simple mixture of RPMI-1640 and 10% fetal calf serum facilitating the successive expansion of stromal cells through multiple passages. bFGF also greatly accelerates the formation of a primary stromal cell layer following inoculation of newly harvested bone marrow cells into dishes. In the presence of bFGF, the stromal cells attain high densities, lose their contact inhibition and grow in multilayered sheets. Heparin greatly potentiates the stimulatory effect of low concentrations of bFGF. The effects of bFGF are fully reversible: cells cultured in the presence of this factor for multiple passages revert to normal growth rates following trypsinization and subculture. A short (4 h) exposure of the cells to bFGF elicits profound growth stimulation. This supports the hypothesis that this factor binds to glycosaminogly-cans in the cell matrix which act as a storage reservoir for this cytokine.     

miR-378对缺血缺氧条件下骨髓间充质干细胞增殖及凋亡的影响

背景：研究miR-378对缺血缺氧条件下骨髓间充质干细胞生长增殖、细胞凋亡等生物学行为的影响,为进一步改善骨髓间充质干细胞在梗死心肌中的生存提供新方法。 目的：观察miR-378转染后的骨髓间充质干细胞耐受缺血缺氧及促进血管形成的能力。 方法：体外培养的骨髓间充质干细胞分为未转染组和转染组,未转染组为未转染miR-378的骨髓间充质干细胞,转染组则采用化学合成的miR-378模拟物转染SD大鼠骨髓间充质干细胞;将两组骨髓间充质干细胞置于缺血缺氧(无血清,体积分数为1%O₂、5%CO₂,94%N₂)环境中培养24 h后,应用锥虫蓝染色计数法、MTS法检测两组细胞在不同时间点的生长及增殖情况,TUNEL法检测细胞凋亡情况;将两组缺血缺氧后的培养基上清液分别刺激人脐静脉内皮细胞,观察血管形成情况。 结果与结论：缺血缺氧干预后48 h和72 h,转染组的骨髓间充质干细胞活细胞数明显高于未转染组(均为P < 0.01);转染组的骨髓间充质干细胞表现出较高的增殖能力,缺血缺氧干预后24 h及48 h细胞增殖升高较未转染组明显,差异有显著性意义(P < 0.01,P < 0.05);缺血缺氧后转染组骨髓间充质干细胞的凋亡比例明显下降(P < 0.05)。两组细胞均可促进血管腔样结构形成,但转染组血管管腔样结构较未转染组显著增多(P < 0.01)。研究结果提示miR-378可促进缺血缺氧后骨髓间充质干细胞的生长增殖并抑制其在缺血缺氧条件下的细胞凋亡,同时可提高其促血管生成的能力。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

骨髓干细胞与神经再生

存在于骨髓内的干细胞来源丰富,采集方法简单,体外扩增容易,具有自体移植的必要条件,是一种理想的种子细胞。目前有研究表明骨髓内干细胞可以分化为神经细胞。这是一种从中胚层向外胚层的跨胚层分化,它挑战了细胞分化的传统观念,因而使这一领域存在着许多争议。     

Infiltrative myelopathy by paracoccidioidomycosis. A review and report of nine cases with emphasis on bone marrow morphology

AIMS: To report nine additional well-defined cases with infiltrative myelopathy by paracoccidioidomycosis (PCM), to describe the specific lesions and infection-related stromal abnormalities, to review the literature on this type of involvement and to introduce a new cause of granulomatous lesions of bone marrow. METHODS AND RESULTS: Different bone marrow specimens were studied (aspirated smears, aspirated clots, biopsy imprints and biopsies) from nine patients with acute or subacute forms of PCM known to have PCM infiltrative myelopathy. CONCLUSIONS: The biopsy specimens were the best for demonstrating bone marrow involvement by PCM. The lesions varied from compact and focal granulomas with few fungal cells to numerous disseminated fungal cells within a loose granulomatous inflammatory reaction, with a continuum between these extremes suggesting a spectrum of immune response to the fungi. Other findings such as bone marrow fibrosis, parenchymal coagulative necrosis and bone necrosis were also observed in the affected areas.     

Distribution of bone marrow cells in the mouse skeleton

Details are given of the distribution of nucleated bone marrow cells in 17 parts of the skeleton of laboratory hybrid mice (CBA x C57BL) weighing 18–21 g. The content of bone marrow in the bones of the spine, head, lower limb, pelvis, upper limb, sternum, and ribs was 33.7, 19.6, 11.9, 8.2, and 9.0% respectively of the total.(Presented by Academician of the Academy of Medical Sciences of the USSR P. D. Gorizontov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 5, pp. 483–485, May, 1979.     

Terminal deoxynucleotidyl transferase-positive cells in trephine biopsies following bone marrow or peripheral stem cell transplantation reflect vigorous B-cell generation

AIMS: Bone marrow is the major site of B-cell generation in humans. While in early childhood a high number of B-cell precursors is found in the bone marrow, only very few such cells are usually detectable in adult bone marrow. To assess the number of immature B cells present after haematopoietic cell transplantation the number of terminal deoxynucleotidyl transferase (TdT)-positive cells in regenerating bone marrow of adult patients was analysed. METHODS AND RESULTS: Bone marrow biopsy specimens were analysed from patients after allogeneic bone marrow transplantation (BMT; n = 14) or stem cell transplantation (SCT; n = 25) and autologous BMT (n = 9). Specimens from 11 untransplanted adult patients and 11 infants were also studied, as negative and positive controls, respectively. Immunohistochemistry was performed on paraffin-embedded bone marrow biopsy sections using TdT as a marker of lymphoid progenitors. Immunoreactivity for CD79a, CD20 and CD10 was used to confirm their B-cell origin. Using computer-assisted automated image analysis we quantitatively assessed the TdT+ cells present. We found a significant increase in the numbers of B-cell precursors in the bone marrow after allogeneic and autologous BMT/SCT compared with adult controls (P = 0.022). To analyse this in detail, we followed some patients after allogeneic BMT/SCT for up to 1445 days, when a marked B-cell increase was still detectable. However, the median number of TdT+ B cells after BMT/SCT was significantly lower than the number of equivalent B cells in infantile bone marrow biopsy specimens (P < 0.001). CONCLUSIONS: Bone marrow of adult patients after BMT/SCT is capable of initiating vigorous precursor B-cell generation, which is not seen in untransplanted adults. However, the increase of immature B cells was variable in our study. Only in two young adult patients did it reach the magnitude of B-cell generation seen in infantile bone marrow where immunocompetent B cells are produced normally. A marked increase in number of immature B cells post-transplant may mimic B-cell acute lymphoblastic leukaemia (B-ALL). This is a potential problem in patients transplanted for B-ALL itself. Since reactive and neoplastic B-cell precursors share the same immunophenotype in paraffin-embedded tissue, additional tools, particularly molecular techniques, may have to be employed to establish the correct diagnosis.     

Human bone marrow-derived IgA is produced by IgA-committed B cellsin vitro

Although human bone marrow has been implicated in the production of serum immunoglobulins, little information is available concerning the kinetics of antibody production (primary- or secondary-type humoral response) or the cells that are responsible for antibody production in human bone marrow. In this study, the kinetics of and cells responsible for antibody production in the bone marrow were investigated. Previous studies have demonstrated that human bone marrow mononuclear cells secrete a significant amount of IgAin vitro. This finding led to the focus of the present investigation on bone marrow IgA production. The results reported here demonstrate that IgA was synthesized de novo in cultures of bone marrow mononuclear cells; its peak concentration in the culture supernatants preceded that of IgM; its production was totally inhibited by the addition of microgram quantities of anti--chain antiserum, while milligram quantities of anti--chain antiserum were required for even partial inhibition of IgA production; and the culture of isolated IgA-bearing cells resulted in a greater than 13-fold increase in IgA concentration in the culture supernatants as compared with those from unseparated bone marrow mononuclear cells. From this study, it was concluded that bone marrow produces IgA as a secondary or anamnestic response to some undetermined stimulus and that IgA-committed B cells residing in, although probably not stimulated in, the bone marrow compartment were responsible for the IgA synthesis and secretionin vitro.     

Frequency of skeletal metastases as revealed by routinely taken bone marrow biopsies

Summary In a total of 581 patients with the presumptive clinical diagnosis of bone marrow metastases, core biopsies of the iliac crest were performed to evaluate the frequency of infiltrates in routinely taken samples. The frequency of metastases depends greatly on the varying clinical indications to perform an examination. Staging procedures will result in a decline in positive findings whereas overt signs and symptoms of tumor spread naturally increase the rates. Thus, the annual rates have decreased from 45 to 28% during the last 5 years. The mean frequency of metastases in 501 patients with known primaries was 24%; related to particular tumors the rates were 49% in prostate, 41% in breast, 19% in thyroid and 7% in bronchogenic cancer. The patterns of bone marrow involvement displayed an overwhelming focal infiltration of the marrow space in carcinomas of the thyroid gland and bronchus, and a more diffuse extension in tumors of the prostate and breast.It was demonstrated that neither the width or the total area of the marrow biopsies nor the site of the core is decisive in determining the yield of positive results, but the length of the cylinder may be. No differences could therefore be observed between Jamshidi's dorsal and Burkhardt's anterior crest biopsy method. The results of histopathology were compared with the findings of total body bone scanning in 209 patients. In 49% of all cases scintigrams showed lesions suggestive of metastatic spread and therefore higher frequency of occurrence than the trephine biopsy. Conversely in 23% of the patients with marrow involvement the scintigrams were negative. It is concluded that the core biopsy of the bone marrow is a most valuable aid for an early detection of bone metastases together with radiological methods and is a basal requirement for clinical staging procedures and choice of therapeutic regimens.     

同种异体骨复合自体骨髓干细胞移植治疗良性骨肿瘤和瘤样病变

背景：同种异体骨是临床常用的骨移植材料,但缺乏诱导成骨能力是最大的问题。 目的：评价良性骨肿瘤及瘤样病变刮除或切除后应用同种异体骨复合自体骨髓干细胞修复骨缺损的效果。 方法：65例良性骨肿瘤(包括瘤样病变)患者,根据植骨情况分为2组。复合骨髓干细胞植骨组35例患者根据预计植骨量从每位患者两侧的髂前上棘或髂后上棘抽取红骨髓20-40 mL,经体外分离、纯化、培养扩增骨髓基质干细胞备用,在植骨前将同种异体骨颗粒与骨髓基质干细胞充分混匀。肿瘤刮除或切除后,将混匀的骨髓基质干细胞与同种异体骨颗粒,植入骨缺损区内。单纯植骨组将用生理盐水浸泡半小时的同种异体骨植入骨缺损区内。分别于治疗后1,3,6,12个月进行植骨区X射线检查,比较两组病例同种异体骨颗粒界限模糊、消失的时间,同时观察术后并发症发生情况。 结果与结论：62例患者均获得12个月以上随访。复合骨髓干细胞植骨组移植骨界限模糊时间和消失时间均短于单纯植骨组(P < 0.05)。复合骨髓干细胞植骨组1例出现排异反应,使用免疫抑制剂治疗2周后痊愈,两组病例均未出现感染。结果表明同种异体骨复合自体骨髓干细胞植骨能明显促进骨融合和骨缺损的愈合。     

Histopathology of bone marrow reconstitution after allogeneic bone marrow transplantation

In order to study haematopoietic reconstitution in allogeneic bone marrow transplantation we investigated bone marrow histology in 61 biopsies of 37 patients, treated with HLA-compatible bone marrow grafts for leukaemia or severe aplastic anaemia. The biopsies were taken from the day of transplantation until 100 d after transplantation. Stromal changes, in particular oedema, fibrosis and granulomas, were found during the whole period of observation. These changes were more prominent in biopsies from leukaemia patients than from patients with aplastic anaemia. The cellularity in the biopsies increased until 28 d after bone marrow transplantation and was stable thereafter. Initially, only clusters of cells belonging to a single cell lineage were seen, suggesting that the first outgrowth of haematopoietic cells is by proliferation of committed precursor cells. Long-lasting abnormalities in localization of haematopoietic cells in the bone marrow space and of the myeloid: erythroid ratio were seen; dyserythropoiesis was common.