脂肪源性间充质干细胞联合造血干细胞共移植治疗顽固性重型再生障碍性贫血2例(英文)1

Henan Tumor Hospital, Henan Institute of Haematology, Zhengzhou 450008, Henan Province, China
CASE INTRODUCTION
Subjects Two child patients with refractory SAA were admitted to Henan Institute of Haematology from August 2002 to December 2007. Patient 1 was an 11-year-old girl diagnosed with SAA. She was transfused with 28 units of packed red blood cells over 6 months and became sensitized to multiple erythrocyte antigens. So she was referred for peripheral blood stem cell (PBS) transplantation from her HLA-identical brother in August 2002. Patient 2 was a repeatedly transfused 12-year-old boy diagnosed with SAA in March 2004 and admitted to our hospital for allogeneic PBSC transplantation in September 2004.
Reagents and instrument Collagenase II (Sigma, St. Louis, MO, USA), fetal calf serum (FCS; Gibco Life Technologies, Paisley, UK), D-MEM/F-12 (Gibco), MCDB-201 (Sigma), insulin transferrin selenium (Gibco), dexamethasone (Sigma), ascorbic acid 2-phosphate (Sigma), epidermal growth factor (Sigma), platelet-derived growth factor BB (Sigma), penicillin (Gibco), streptomycin (Gibco), ATG (Upjohn, Kalamazoo, MI, USA).
中国组织工程研究与临床康复 第 13 卷 第 36 期 2009–09–03 出版 Journal of Clinical Rehabilitative Tissue Engineering Research September 3, 2009 Vol.1e
Zhang Gong-li, Li Ning, Song Yong-ping, Lin Quan-de, Wei Xu-dong, Fang Bai-jun
Abstract: To assess the efficacy of cotransplantation of haploidentical mesenchymal stem cells (MSC) and hematopoietic stem
separately originated from haploidentical mother and peripheral blood stem cells (PBSCs) from HLA-identical sibling brother or sister of patients. The patient 1 received a cotransplantation of PBSCs and AMSCs (1 × 106/kg) at a dose of 4.5 × 108 mononuclear cells/kg (containing 4.41×106 CD34+ cells/kg and 0.11×105 CD3+ cells/kg); the patient 2 received a second PBSCT at a dose of 6.5 × 108 mononuclear cells/kg (containing 4.62×106 CD34+ cells/kg and 0.12×105 CD3+ cells/kg) and AMSC (1 × 106/kg) from his
haploidentical mother. The results show that the cotransplantation was successful. During the two years of follow up, the two patients
exhibited good condition, with no other treatment or transfusion dependence.
cells (HSC) in the treatment of refractory severe aplastic anemia, Two child patients with refractory severe aplastic anemia admitted
to Henan Institute of Haematology from August 2002 to December 2007 were selected. Adipose tissue-derived MSCs (AMSCs) were
Methods AMSC preparation With the approval of ethics committee at Henan Tumor Hospital and informed consent from the two haploidentical mothers, AMSCs were isolated respectively according to previously described method[20]. Briefly, abdominal subcutaneous adipose tissue obtained from the donor was digested with 0.2% collagenase II for 30 minutes under constant shaking. After removal of the floating mature adipocytes and erythrocytes, the low layer was centrifuged at 200 g for 10 minutes. After successive filtrations through 100and 70-µm sieves, the cells were washed with phosphate buffered saline/2% fetal calf serum (FCS)
Cotransplantation of haploidentical mesenchymal stem cells and hematopoietic stem cells in the treatment of two child patients with refractory severe aplastic anemia*★
INTRODUCTION
Results of hematopoietic stem cell transplantation (HSC) for patients with acquired severe aplastic anemia (SAA) have improved considerably over the last decades[1]. However, a large amount of retrospective analyses suggest that graft failure remains one of the important, life-threatening complications[2]. The Registry of the European Blood and Marrow Transplantation shows that for patients receiving human leukocyte antigen (HLA)-identical sibling grafts, there has been a modest reduction of graft failure over time: 18% before 1980, 12% from 1980 to 1990, and 11% from 1991 to 1998 (P = 0.12) [3]. Over several decades, various transplant strategies have been introduced to decrease graft failure, with mixed success [2,4-7]. Human mesenchymal stem cells (MSC) have been shown to promote engraftment of cord blood-derived HSC in immunodeficient mice, fetal sheep, and almost patients [8-13]. Furthermore, MSCs have been observed to alter lymphocyte reactivity to allogeneic target cells and tissues, which leads to permanent donor-specific immunotolerance in allogeneic host and results in long-term allogeneic skin graft acceptance [14-15]. In vivo, in humans, autologous and allogeneic MSCs are safe to infuse with no acute adverse events or long-term MSC-associated adverse events [11,16-19]. These results further support the hypothesis that the infusion of culture-expanded MSCs, together with HSC transplantation, is a safe procedure and could potentially lead to a reduction of graft failure and a fast speed of engraftment after myeloablative treatment. This study used haploidentical adipose tissue-derived MSCs (AMSCs) to enhance engraftment and to prevent rejection, as well as to reduce the risk of graft failure in two children with SAA.