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 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）.

Granulocyte-macrophage colony stimulating factor improves cardiac function in rabbits following myocardial infarction

Objective: To investigate the therapeutic potency of recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in a rabbit myocardial infarction model. Methods: A myocardial infarction was created by the ligation of the major ventricular branch of the left coronary artery in rabbits. After myocardial infarction, the animals were randomly assigned to GM-CSF treatment group, untreated groups and sham-operated group. The rabbits of the treated group were injected into GM-CSF by subcutaneous administration, 10 μg/kg/day, once a day for 5 days. The untreated and sham-operated group received a equal saline in the same manner as treated group. Six weeks later echocardiography and haemodynamic assessment were undertaken to assesse cardiac function. The size of the infarct region of the heart were also studied. Results: The untreated group exhibited significant higher left ventricle end-diastolic pressure, higher central venous pressure, and with significant lower mean blood pressure, lower peak first derivative of left ventricle pressure (dP/dt) than the sham group. Also, Rabbits in untreated group display significant systolic dysfunction shown by the decreased ejection fraction, diastolic dysfunction shown by increasing in the ratio of E wave to A wave (E/A), and display left ventricle enlargement. However, GS-CSF singnificantly prevented heart dysfunction, left ventricle enlargement, and reduced infarct size in treatment group. Conclusion: Administration GM-CSF after cardiac infarction can improve heart function. These findings indicate the technique may be a novel and simple therapeutic method for ischemic myocardium.

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.

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.