Dl-3-butylphthalide-enhanced hematopoietic stem cell transplantation and endogenous stem cell mobilization for the treatment of cerebral infarcts

Exogenous stem cell transplantation and endogenous stem cell mobilization are both effective for the treatment of acute cerebral infarction. The compound dl-3-butylphthalide is known to improve microcirculation and help brain cells at the infarct loci. This experiment aimed to investigate the effects of dl-3-butylphthalide intervention based on the transplantation of hematopoietic stem cells and mobilization of endogenous stem cells in a rat model of cerebral infarction, following middle cerebral artery occlusion. Results showed that neurological function was greatly improved and infarct volume was reduced in rats with cerebral infarction. Data also showed that dl-3-butylphthalide can promote hematopoietic stem cells to transform into vascular endothelial cells and neuronal-like cells, and also enhance the therapeutic effect on cerebral infarction by hematopoietic stem cell transplantation and endogenous stem cell mobilization.

The more, the less： age and chemotherapy load are predictive of poor stem cell mobilization in patients with hematologic malignancies

Background Intensive treatment such as autologous peripheral blood stem cell （PBSC） transplantation is an important therapeutic strategy in many hematologic malignancies.A number of factors have been reported to impact PBSC mobilization,but the predictive factors varied from one study to another.This retrospective study assessed our current mobilization and collection protocols,and explored the factors predictive of PBSC mobilization in patients with hematologic malignancies.Methods Data of 64 consecutive patients with hematologic malignancies （multiple myeloma,n=22; acute leukemia,n=27; lymphoma,n=15） who underwent PBSC mobilization for over 1 year were analyzed.Four patients with response to treatment of near complete remission or better were administered granulocyte colony-stimulating factor （G-CSF） to mobilize PBSCs.Sixty patients received G-CSF followed by chemotherapy mobilizing regimens.Poor mobilization （PM） was defined as when ≤2.0×106 CD34＋ cells/kg body weight were collected within three leukapheresis procedures.Results The incidence of PM at the first mobilization attempt was 19% （12/64）.The PM group was older than the non-PM group （median age,51 vs.40 years; P=0.013）.In univariate analysis,there were no significant differences in gender,diagnosis,and body weight between the PM and non-PM groups.A combination of chemotherapy and G-CSF was more effective than G-CSF alone as a mobilizing regimen （P=0.019）.Grade Ⅲ or Ⅳ hematopoietic toxicity of chemotherapy had no significant effect on the mobilization efficacy.Supportive care and the incidence of febrile neutropenia were not significantly different between the two groups.In multivariate analysis,age （odds ratio （OR）,9.536;P=-0.002） and number of previous chemotherapy courses （OR 3.132; P=0.024） were two independent negative predictive factors for CD34＋ cell yield.PM patients could be managed well by remobilization.Conclusion Older age and a heavy load of previous chemotherapy are the negative risk factors for PBSC mobilization.

The Mobilization of Autologous Bone Marrow Stem Cells in the Treatment of Heart Failure with Chinese Medicine

Heart failure （HF） is a severe heart disease. The use of autologous bone marrow stem cells （BMCs） mobilization in the treatment of HF has been a hot topic to research both in Western medicine and Chinese medicine （CM）. There are many clinical trials and experiments on study of BMCs mobilization for HF therapy, including integrative medicine. The effect of BMCs mobilization is favorable for cardiac repair, while some advantages of CM support the advanced study of its application in BMCs mobilization to treat HF. In addition, with mechanisms of autologous BMCs mobilization for the treatment of HF that will be revealed in the future, especially stem cells niches, integrative medicine would play an important role in this clinical thought of therapy model gradually. Simultaneously, CM should adapt the new approaches of stem cells progresses on HF treatment as holding characteristics of itself.

Zebrafish Cdh5 negatively regulates mobilization of aorta-gonad-mesonephros-derived hematopoietic stem cells

Establishment of a hematopoietic stem cell（HSC）pool depends on the appropriate formation,maturation and mobilization of HSCs in vertebrates.In mice,the aorta-gonad-mesonephros（AGM）is a prominent site for the formation of definitive HSCs from endothelial cells,although the placenta and yolk sac also give rise to HSCs（Mikkola and Orkin,2006;Chen et al.,2009）.After formation,AGM-derived HSCs migrate to the fetal liver（FL）,and ultimately to the bone marrow （BM）, two definitive hematopoietic organs （Cumano and Godin, 2007）.

Role of adhesion molecules in mobilization of hematopoietic cells

To study the changes of adhesion molecules' expressions during the recombinant h u man granulocyte colony stimulating factor (rhG CSF) mobilization in periphera l blood stem cell transplantation (PBSCT), and to confirm the influence of rhG CSF on hematopoietic stem cells, which are proposed to guide mobilization in PBS CT Methods Mice were injected subcutaneously with diluted rhG CSF or normal saline for 7 d ays The blood Sca 1 + stem cell count and bone marrow (BM) nucleated cell co unt were enumerated The expressions of CD49d and CD44 and the adhesive ability of mononuclear cells to bone marrow matrix (fibronectin) were examined by flow c ytometry and 51 Cr adhesive assay, respectively Results The mobilizing effect of rhG CSF on mice was the same as on humans The number of Sca 1 + cells in peripheral blood reached the peak on the seventh day, the BM nucleated cell count was reduced, and the expressions of CD49d and the cells ' adhesive ability in BM and PB declined Conclusions rhG CSF can reduce some cell adhesion molecules' expressions and the adhesive a bility of hematopoietic stem cells to BM matrix, therefore mobilizing hematopoie tic stem cells (HSC) from the BM to the peripheral blood

Negative association of donor age with CD34＋ cell dose in mixture allografts of G-CSF-primed bone marrow and G-CSF-mobilized peripheral blood harvests

Background The effects of donor characteristics on CD34＋ cell dose remain controversial. Recently, we developed a novel haploidentical transplant protocol, in which mixture allografts of granulocyte colony-stimulating factor （G-CSF）- primed bone marrow （G-BM） and G-CSF-mobilized peripheral blood （G-PB） were used. The aim of this study was to investigate the effects of donor characteristics on CD34＋ cell dose in mixture allografts of G-BM and G-PB. Methods A total of 162 healthy adult donors, who underwent bone marrow harvest and peripheral blood collection between January 2009 and November 2010 in Peking University People＇s Hospital, were prospectively investigated. G-CSF was administered subcutaneously at a dose of 5 pg/kg once a day for 5-6 consecutive days. Bone marrow and peripheral blood stem cells were harvested on the fourth day and fifth day, respectively. A final total CD34＋ cell dose less than 2× 106 cells/kg recipient body weight was considered a poor mobilization. Results Of the 162 donors, 31 （19.1%） did not attain this threshold. The obtained median CD34＋ cell doses in bone marrow, peripheral blood, and mixture allografts were 0.83×106/kg, 2.40×106/kg, and 3.47×106/kg, respectively. Multiple regression analysis showed that donor age had a significant negative effect on CD34＋ cell dose in either G-BM, or G-PB, or mixture allografts of G-BM and G-PB. And a 1-year increase in age was associated with a 5.6% decrease in the odds of achieving mobilization cutoff. No significant correlation was found for donor gender, body mass index （BMI）, and weight. Conclusion Donor age is the only factor among the four parameters, including age, gender, weight, and BMI, that influence CD34＋ cell dose in mixture allografts of G-BM and G-PB, and younger donors should be chosen to obtain sufficient CD34＋ cells for transplantation.