1.Clinical report on nonmyeloablative autologous peripheral blood stem cell transplantation for systemic lupus erythematosus by using different conditioning regimens
Jingbo XU ; Wenzheng PANG ; Xuegang LI ; Feng XIE ; Shuping ZHONG ; Jiangnan REN ; Lijun HOU
Chinese Journal of Rheumatology 2012;16(8):527-531
Objective To compare the clinical efficacy and safety of two different conditioning regimens in nonmyeloablative autologous peripheral blood stem cell transplantation (NAST) for the treatment of systemic lupus erythematosus (SLE).Methods Different conditioning regimens were used in two groups:cytarabin combined cyclophosphamide in group 1 and ATG combined cyclophosphamide in group 2.Different recovery time of leucocytes,neutrophils and platelets in the two groups were compared.Statistical analysis were carried out by paired t-test.Results The mean time for peripheral leucocytes reaching 1.0×109/L,neutrophils getting up to 0.5×109/L,platelet raising to 100×l09/L and hemoglobin rising to 120 g/L in group 1 were [(7.2±1.3),(8.0±1.5),(10.5±1.4),(22.1±2.3)days] and [(10.4±2.1),(12.0±1.9),(19.3±2.1),(28.1± 2.4)] days in group 2.The difference was statistically significant (P<0.01).CD4+ cell count and the ratio of CD4+/CD8+ of pre- and pro-NAST was changed.No significant differences were observed in the two groups.Conclusion For the sake of safety and hematopoietic reconstitution,we recommend cytarabin combined cyclophosphamide as the preferred conditioning regimen.
2.Establishment of a severe aplastic anemia mouse model by using recombinant human interferon-gamma plus busulfan
Xiang LIU ; Shuping ZHONG ; Lijun HOU ; Feng XIE ; Xuegang LI ; Wenzheng PANG ; Jingbo XU ; Zhiguo HE
Chinese Journal of Tissue Engineering Research 2014;(36):5868-5873
BACKGROUND:It is important to establish an ideal mouse model of severe aplastic anemia for investigating the mechanism and finding new therapies for aplastic anemia. OBJECTIVE:To establish a severe aplastic anemia mouse model by using recombinant human interferon-γand busulfan. METHODS:Sixty healthy Kunming female mice were randomly divided into two groups:model group (n=50) and control group (n=10). The model group was given recombinant human interferon-γat a dose of 1×104 U/d by intraperitoneal injection and busulfan at a dose of 18 mg/(kg·d) through stomach feeding for 7 days. The same volume of physiological saline was given to control group. Multi-parameters, including general condition, body weight, blood cellcount, morphology and biopsy of bone marrow were analyzed in two groups. RESULTS AND CONCLUSION:At day 7 after treatment, the weight, white blood cellcount, hemoglobin, blood platelet, reticulocyte count in model group were significantly lower than control group (P<0.05). Bone marrow smears and biopsy of model group showed marked reduction of bone marrow proliferation and increases of percentages of non-hematopoietic cellclusters and adipose tissue. The oil drop and fat vacuole were apparently seen in the model group. Severe aplastic anemia mouse model can be established by using recombinant human interferon-γand busulfan successful y, which is economic, stable and easy to operate.
3.Nonmyeloablative autologous peripheral blood stem cell transplantation for refractory autoimmune disease: 5-year follow-up
Jingbo XU ; Feng XIE ; Wenzheng PANG ; Shuping ZHONG ; Xuegang LI ; Jiangnan REN ; Lijun HOU
Chinese Journal of Rheumatology 2012;16(2):129-131
Objective To investigate the long-term efficacy of nonmyeloablative autologous peripheral blood stem cell transplantation(NAST) to cure refractory autoimmune disease(AD).MethodLong-term follow up of four cases of AD patients with NAST were summarized.The pretreatment regimen was intravenous injection of cytarabin (200 mg· kg-1· d-1 ) and cyclophosphamide (40 mg· kg-1· d-1).The therapeutic effect was evaluated by the change of symptoms and signs and long term complications.Changes of immune function were detected by flow-cytometry.ResultsFive cases of patients had been successfully engrafted.The average time for peripheral leucocytes count to reach 4.0×109/L was 12 days.It needed 10 days for platelets to return to 100×109/L and 22 days for hemoglobin to 120 g/L.Apparent remission of symptoms and signs was observed after transplantation.Lymphocyte subtypes analysis pre- and post- NAST showed that count of CD4+ and the ratio of CD4 +/CD8 + was returned to normal.One patient gave birth to a healthy baby four years after transplantation.Three female patients returned tonormal life. Conclusions Compared with classical myeloablative stem cell transplantation,NAST has a rapid hematopoietic recovery and good long-term therapeutic effect in AD.The quality of life in AD patients treated with NAST is higher than those treated with myeloablative hematopoietic stem cell transplantation.
4.The platelet activation and the expression of interleukin-1β in patients with rheumatoid arthritis
Shuping ZHONG ; Linjuan ZENG ; Xuegang LI ; Zhiguo HE ; Wenzheng PANG ; Feng XIE ; Lijun HOU ; Jingbo XU
Chinese Journal of Rheumatology 2014;(10):697-699
Objective To evaluate the significance of platelet activation and the expression of inter-leukin (IL)-1β in patients with RA. Methods The activation of platelets and the expression of IL-1β in pla-telets in 50 RA patients(22 high-active, 28 mediate/low active ) and 30 normal controls were determined us-ing flow cytometry. Meanwhile, inflammatory indicators such as erythrocyte sedimentation(ESR), C-reactive protein (CRP) and DAS28 were also recorded. T test and correlation analysis were performed. Results The platelet activation in RA group(19.2±4.8) was higher than the control group(9.0±2.9)(t=10.5, P=0.001). The expression of IL-1β in platelets in RA group(41±11) was higher than control group(21±8)(t=9.01, P =0.000) .The platelet activation in high-active RA group(22 ±4) was higher than mediate/low active RA group(17 ±4)(t =3.96,P =0.001). The expression of IL-1β in platelets in high-active RA group(45 ±10) was higher than mediate/low active RA group (38 ±10)(t =2.329,P =0.024). The expression of IL-1β in platelets in RA group was positively correlated with the level of ESR、CRP and DAS28 (r value and P value were 0.576, 0.578, 0.618 and 0.000, 0.000, 0.000 respectively). Conclusion The platelets of patients with RA are activated and may suggest that IL-1β, which may associate with disease activity. Our research suggest that platelet may play a role in the inflammatory process of RA by secreting IL-1β.
5.Transplantation of bone marrow mononuclear cells from polycythemia vera patients into aplastic anemia mice
Shuping ZHONG ; Jing TIAN ; Xiang LIU ; Lijun HOU ; Zhiguo HE ; Jingbo XU ; Xuegang LI ; Feng XIE ; Wenzheng PANG ; Anqi LIANG
Chinese Journal of Tissue Engineering Research 2015;(23):3705-3710
BACKGROUND:As the high proliferation and low apoptosis of the bone marrow in polycythemia vera patients, hematopoietic stem cels transplanted into NOD/SCID mice can differentiate into erythroid cels, but whether hematopoietic stem cels transplantation could improve the hematopoietic function of aplastic anemia mice is not yet reported. OBJECTIVE:To investigate whether transplantation of bone marrow mononuclear cels with JAK2V617F mutation from polycythemia vera patients can influence hematopoietic reconstruction in aplastic anemia mice. METHODS:Severe aplastic anemia mouse models were established by using recombinant human interferon-γplus busulfan, and then, these mouse models were randomly divided into experimental group (n=10) and control group (n=10). Bone marrow mononuclear cels isolated from polycythemia vera patients with positive JAK2V617F mutation were transplanted into the mice in the experimental group via tail vein at 5 days after drug withdrawal.The same volume of normal saline was administered to the control group. Routine peripheral blood test, morphology of bone marrow cels, bone marrow biopsy, and percentage of CD45+ cels in the peripheral blood and marrow were determined at 14 days after transplantation. RESULTS AND CONCLUSION: At 14 days after transplantation, pancytopenia occurred in the experimental group, bone marrow smears showed scattered lymphocytes and hematopoietic progenitors, and bone marrow biopsy presented that hematopoietic tissues were reduced and a smal amount of granulocyte cels and erythroblasts could be seen, but megakaryocytes were rare. In contrast to the control group, there was no improvement in the hematopoietic function of mice in the experimental group. CD45+ cels were detectable in the peripheral blood and bone marrow in the experimental group, but not in the control group; and a higher percentage of CD45+ cels was measured in the bone marrow than in the peripheral blood of experimental group mice. Experimental findings indicate that bone marrow mononuclear cels from polycythemia vera patients with positive JAK2V617F mutation can be engrafted into aplastic anemia mice, but cannot improve the hematopoietic function of mice.