Janczewska S, Ziolkowska A, Durlik M, Olszewski W L, Lukomska B
Surgical Research and Transplantology Department, Medical Research Center Institute, Polish Academy of Sciences, Warsaw.
Transplantation. 1999 Jul 27;68(2):201-9. doi: 10.1097/00007890-199907270-00007.
Bone marrow (BM) transplantation for treatment of hematological and solid malignancies is routinely carried out in conjunction with radio- and chemotherapy. Many patients achieve complete remission of the malignant process; however, their lymphohematopoietic recovery remains in most cases incomplete. This is probably due to the functional changes in the recipient BM stromal cells subsequent to myeloablative therapy. Transplantation of BM hematopoietic cells in a spatial relationship with stromal cells would give an insight into the kinetics of hematological repopulation of the recipient. The aim of this study was to investigate the lymphopoietic reconstitution of irradiated rats after vascularized bone marrow transplantation (VBMT) in comparison with i.v. bone marrow cell (BMC) infusion.
Lewis rats were totally irradiated with 8Gy and repopulated with syngeneic BMC introduced i.v. or in orthotopic hind limb graft. Ten days after irradiation and BMC graft BM, peripheral blood (PB) and mesenteric lymph nodes (MLN) were collected. The yield and the phenotype of cells were analyzed.
VBMT brings much higher cell repopulation of BM cavities of lethally irradiated rats than BMC infusion. Orthotopic hind limb graft promotes also rapid lymphocyte replenishment of PB and MLN of lethally irradiated syngeneic recipients. The population rate of BMC, PB lymphocytes, and MLN lymphocytes was higher after VBMT than BMC injection in suspension. The percentage of T and B lymphocytes in PB and MLN on day 10 after VBMT was comparable with control values. Reconstituted PB lymphocytes showed two subsets of CD4+ cells: "bright" and "dull." All CD4+ cells in PB lymphocytes of i.v. BMC infused recipients expressed low level of these molecules ("dull" subset).
The results of our studies indicate that the presence of stromal cells in their close relationship with stem cells is essential for the fast lyphohematopoietic repopulation of irradiated recipients. The population of CD4+dull cells may represent immature cells. These cells were not found in MLN of VBMT rats. All MLN CD4+ cells represented the "bright" subset, what suggests that the process of cell maturation may occur in the lymphoid organs.
骨髓移植用于治疗血液系统恶性肿瘤和实体瘤时，通常与放疗和化疗联合进行。许多患者实现了恶性病程的完全缓解；然而，在大多数情况下，他们的淋巴细胞造血恢复仍不完全。这可能是由于清髓治疗后受体骨髓基质细胞的功能发生了变化。将骨髓造血细胞与基质细胞按空间关系进行移植，将有助于深入了解受体血液学再填充的动力学。本研究的目的是比较血管化骨髓移植（VBMT）与静脉内输注骨髓细胞（BMC）后，受照射大鼠的淋巴细胞重建情况。
将Lewis大鼠用8Gy进行全身照射，然后通过静脉内或原位后肢移植输入同基因BMC进行再填充。照射和BMC移植后10天，采集外周血（PB）和肠系膜淋巴结（MLN）。分析细胞的产量和表型。
与BMC输注相比，VBMT能使受致死性照射大鼠的骨髓腔有更高的细胞再填充。原位后肢移植也促进了受致死性照射的同基因受体的PB和MLN中淋巴细胞的快速补充。VBMT后BMC、PB淋巴细胞和MLN淋巴细胞的增殖率高于悬浮状态下的BMC注射。VBMT后第10天，PB和MLN中T和B淋巴细胞的百分比与对照值相当。重建的PB淋巴细胞显示出CD4+细胞的两个亚群：“亮”和“暗”。静脉内输注BMC的受体的PB淋巴细胞中的所有CD4+细胞均表达这些分子的低水平（“暗”亚群）。
我们的研究结果表明，基质细胞与干细胞的密切关系对于受照射受体的快速淋巴细胞造血再填充至关重要。CD4+暗细胞群体可能代表未成熟细胞。在VBMT大鼠的MLN中未发现这些细胞。所有MLN CD4+细胞均代表“亮”亚群，这表明细胞成熟过程可能发生在淋巴器官中。
