bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of Human Umbilical Cord Blood Mesenchymal Stem Cells into Nerve-Like Cells by Salvia Miltiorrhiza.
Authors: Ma Lian , Feng Xueyong , Yang Liye , Luo Minjie , Xie Qingdong , Huang Tianhua 
Published: October 2019

Abstract
Salvia miltiorrhiza is a traditional Chinese herb with thousands of years history. Composite salvia injection (CSI), a widely used administration in China nowadays, consists of Salvia miltiorrhiza, notoginseng, radix and borneo. It can promote blood flow, but also regulate qi to alleviate pain. So it is frequently used for angina, coronary heart disease and chest discomfort. Recently, some laboratory studies show that CSI may have the effect of cell induction.. In this study, we aim to investigate its neural induction.
Objective: To investigate the differentiation-inducing effects of salvia miltiorrhiza on umbilical cord blood mesenchymal stem cells.
Methods: The immunophenotypes of human umbilical cord blood-derived mesenchymal stem cells(MSCs) were determined by flow-cytometry. Salvia miltiorrhiza was adapted to induce the differentiation of the primary cultured cells of umbilical cord blood and MSCs. The results were compared with nerve growth factor(NGF) and ganglioside(GM1). The differentiated and undifferentiated cells were identified with immunocytochemistry.
Results: In primary culture, certain cells proliferated and formed cell clusters. These cells were either fibroblast-like or round in shape with various sizes. The positive rates for MSCs phenotypes CD29, CD44, CD59 of primary culture cells were 10.7%,37.27% and 66.67%, respectively. Salvia miltiorrhiza could induce the primary cultured cells of umbilical cord blood to express neural phenotypes. After passage, the MSCs could be maintained in vitro for extended periods with stable population doubling. The positive rates for CD29, CD44, CD59 of human umbilical cord blood-derived MSCs were 40.2%,70.5% and 95.4%, respectively. Salvia miltiorrhiza could induce the MSCs to express three kinds of proteins: nestin(the marker of neuronal precursor stem cells), β-TubulinIII and neurofilament (NF) (the marker of neuronal phenotypes) and glial fibrillary acidic protein(GFAP, the marker of astrocyte). Besides, NGF and GM1 could also induce the same MSCs to nerve-like cell, which could express the same markers: β-TubulinIII, NF and GFAP. In comparison NGF and GM1, the induction effect of salvia miltiorrhiza demonstrated the higher rate of expressing neuron phenotypes at a faster speed.
Conclusion: The human MSCs could be isolated from human umbilical cord blood. Salvia miltiorrhiza can induce the MSCs to differentiate into nerve-like cells, therefore, might act as a potential drug for neural induction.
Mesenchymal Stem Cells Modulates Differentiation into Hepatocyte Cell in VX2 Implanted Rabbit Liver Cancer Model.
Authors: Ren Jun , Wang Xiaodong , Di Lijun , Yang Renjie , Jiang Hanfang , Hu Weiheng 
Published: October 2019

Abstract
The issues of differentiation of mesenchymal stem cells still remain great increasing interests for the last recent years. For non-hemotological malignancies could these pluripotential stem cells be served as surrogates for the reconstruction of cell and organ function when solid carcinoma occurred or metastasized. New Zealand rabbits liver cancer model with squamous cells of VX2 implanted were used to explore the possibilities of mesenchymal stem cell into the hepatocytes. The results showed that there were abundant dispersed small roundness cells with mononuclear or binuclear were found in portal areas of normal liver lobes after mesenchymal stem cells had been implanted at 4 weeks, and those were originated from mesenchymal stem cells without expression of albumin, CK18 and CK19 by confocol laser microspopy; but the arrangement of partial hepatic cords was disordered near the portal areas of normal liver lobes, the cells was small like as renewal cells expressing albumin, Ck18 and CK19. It is hopefully firstly provided the evidence that mesenchymal stem cell could have the abilities and modulate the differentiation of hepatocytes which secreting albumin as well as CK18, CK19, but did not differentiate into cancer cells.
Amiodarone- Induced Bone Marrow Granulomas.
Authors: Mohamed Tarek , Sycheva Tatyana , Aish Leo , Schneider Douglas , Oo Thein H. 
Published: October 2019

Abstract
INTRODUCTION: Amiodarone is associated with several adverse effects, including hematologic side effects such as pancytopenia, hemolytic anemia and aplastic anemia. Very few cases of amiodarone-induced bone marrow granulomas have been reported.
METHODS: We report 2 cases of amiodarone-induced bone marrow granulomas. Patient 1: 81-year-old male presented with leukopenia, thrombocytopenia, and hepatosplenomegaly after 2 years of amiodarone. Patient 2: 80-year-old male presented with pancytopenia 2 ½ years after starting amiodarone. Examination was unrmarkable. Bone marrow biopsies on both patients showed non-caseating granulomas with negative stains for acid-fast bacilli and fungi. Both had normal CBC before amiodarone therapy. The literature was reviewed for amiodarone-induced bone marrow granulomas on MEDLINE.
RESULTS: There are 8 cases of amiodarone-induced bone marrow granulomas in the literature. Male: female - 5:3. One also had amiodarone-induced hepatic granulomas. Amiodarone was stopped in 5 cases with the improvement of granulomas in 3 cases. Patient characteristics and outcomes are shown below.
Ref Age/Sex CBC/Chemistry abnormalities Associated blood disorders Amiodarone stopped outcome/Note Boutros et al 67M none MGUS Yes fewer granulomas in bone marrow Boutros et al 77F platelet ↓ none Yes platelet count normalized and fewer granulomas in bone marrow Rosenbaum et al 53/F WBC ↑, Platelet ↑ myelofibrosis No also has amiodarone-induced hypothyroidism Rosenbaum et al 78/F RBC ↓ Yes Doing well. CBC unknown Mukhopadhyay et al 81/M RBC ↓ MDS No Erythropoetin improved anemia Mukhopadhyay et al 62/M pancytopenia none No Also has splenomegaly. CBC stable Yamreudeewong et al 63/M Unknown none Yes Bone marrow biopsy performed for fever of unknown origin. Symptoms improved. Moran et al 76/M RBC ↓, LFT ↑ MGUS Yes Bone marrow granulomas resolved. Liver biopsy showed granulomas. Our patient 1 81/M WBC ↓, Platelet ↓ none Yes Also has amiodarone-induced hyperthyroidism. Hepatosplenomegaly and CBC stable Our Patient 2 80/M Pancytopenia none No Erythropoetin improved anemia
CONCLUSION: Bone marrow granulomas, although rare, should be considered as a differential diagnosis in patients on amiodarone presenting with cytopenias.
Cellular Iron Metabolism Studies Demonstate Safety of Magnetic Tracking of Mesenchymal Stem Cells.
Authors: Pawelczyk Edyta , Arbab Ali S. , Pundit Sunil , Frank Joseph A. 
Published: October 2019

Abstract
Background: Ferumoxides-protamine sulfate (Fe-Pro) complexes are used for intracellular magnetic labeling of mesenchymal stem cells (MSCs) to non invasively monitor cell trafficking and tissue distribution by in vivo magnetic resonance imaging (MRI). It has been previously shown that there was no short or long- term toxic effects on cell’s viability, proliferation, reactive oxygen species and biological functions including differentiation capacity of MSCs, however the effects of dextran coated superparamagnetic iron oxide (SPIO) nanoparticles labeling on cellular iron metabolism and storage is unknown.
Objective: Evaluate the effect of using Fe-Pro complexes for magnetic cell labeling in MSCs on the expression of transferrin receptor (TfR-1) and ferritin, proteins involved in intracellular iron metabolism and storage.
Methods: Confluent MSCs were labeled with Fe-Pro complexes at the ratio of 100 ug/mL to 6 ug/mL. After labeling, cells were washed and cultured for 2 months. TfR-1 and ferritin expression were evaluated at the gene and protein levels in total cell lysates, on day 1, 3, 7, 14, 28 and 35 days post-labeling, by real-time polymerase chain reaction (RT-PCR) and Western blotting. MSCs were evaluated for the presence of iron by Prussian blue stain and light microscopy. In addition, TfR-1 and ferritin levels were determined for Fe-Pro labeled and unlabeled MSCs, allowed to slowly multiply, as a result of dividing the cells in half when they reached confluence.
Results: All cells were Prussian blue positive on light microscopy following labeling with Fe-Pro. Labeling of MSCs grown to confluence resulted in short-term increase of TfR-1 mRNA (day 1 and day 3, p= 0.0056) without changes in TfR-1 protein levels. Fe- Pro labeled MSC demonstrated an increase in ferritin gene expression on day 7 and 14 (p=0.0003) compared to unlabeled cells, while protein levels were higher compared to unlabeled MSC at each time point (p=0.005). However, ferritin protein levels from Fe-Pro labeled MSCs were not significantly increased after 7 passages.
Conclusions: Magnetic labeling of cells with FDA approved ferumoxides complexed to protamine sulfate elicited short-term changes in cellular iron metabolism and storage that was dependent on ability to divide. Fe-Pro labeling did not have any long-term implications validating the safety of Fe-Pro labeling technique for MSCs trafficking studies by MRI.
Anatomical Compartments Modulate the Response of Human Hematopoietic Cells to Mitogenic Signaling, In Vivo.
Authors: Wang Linlin , Nagasawa Yasuo , Wood Brent , Lintmaer Ingrid , Guo Wenjin , Harkey Michael , Papayannopoulou Thalia , Nourigat Cynthia 
Published: October 2019

Abstract
Hematopoietic cells can respond differently to a mitogenic signal depending on whether the signal is delivered in vitro or in vivo. Results presented here suggest that the compartment in which a human hematopoietic progenitor resides can influence its response to a proliferative stimulus. An ectopically expressed conditional derivative of the thrombopoietin receptor (F36VMpl) in human cord blood CD34+ cells induces, upon provision of an agonist ligand, the differentiation (but not expansion) of transduced human burst forming units erythroid (BFUe) in culture. Here we show that upon transplantation into immune deficient mice, F36VMpl-expressing human BFUe and multipotential mixed progenitors (CFU-mix) decline in the marrows of ligand-exposed mice, replaced by a 12–17 fold expansion of differentiated erythroid precursors. In contrast, F36VMpl signaling dramatically expands BFUe and CFUmix in the spleen. Clonal analysis is consistent with the interpretation that F36Vmpl signaling induces an in situ expansion of BFUe and CFUmix in the spleen. In aggregate, these findings suggest that differences in environmental signals present in the marrow versus spleen can regulate the differentiation versus expansion of BFUe and CFU-mix.
Myeloablative Single Cord Transplants (SCT) Versus Dual Cord Transplants (DCT) in Adults with Acute Leukemia.
Authors: Creer Michael H. , Regan Donna , Alonso Mario , Wooford Jonathan 
Published: October 2019

Abstract
Background: Combining 2 cord blood products overcomes the total nucleated cell (TNC) dose limitation and may improve clinical outcomes following allogeneic cord blood (CB) transplantation in adults. We performed a retrospective case-control study in adult patients with acute leukemia receiving myeloablative conditioning and 1 or 2 cord blood units to identify potential causes for differences in clinical outcomes following SCT and DCT and product characteristics predictive of long-term engraftment in DCT recipients.
Study Design: To evaluate 20 DCT cases, we selected 20 SCT with the largest TNC dose as controls from a cohort of 103 adult SCT patients. SCT and DCT were matched for age, sex, diagnosis, disease status, ethnicity and body weight (0.11 ≤ p ≤ 0.78) excluding patients with graft failure or previous transplants.
Results: Administered TNC dose for DCT (3.7x10e7/kg) was nearly 2-fold greater than SCT (1.9x10e7/kg, p < 0.0001) with no significant differences in post-thaw TNC recovery (p=0.13). Time to ANC > 500/uL for DCT was 17 days compared to 20 days for SCT (p<0.02). For SCT, there were 9 and 11 pts. with 1 or 2 Ag mismatch (molecular) at HLA-A,B or DRB1, respectively, (mean = 1.6 Ag mismatch). Three-way comparison of both donors and recipient for DCT also gave mean = 1.6 Ag mismatch (molecular). Overall survival (OS) at 12 months was 18% for SCT and 72% for DCT (p<0.0001) with median duration of follow-up of > 18 mos. for both groups. OS was significantly correlated with post-thaw TNC dose for SCT (p<0.04) but not for DCT (p=0.88). In the first 100 days post-transplant, infection rates for SCT (65%) and DCT (50%) were similar with no significant differences in frequency of viral, fungal or bacterial infections (p=0.74). Most importantly, infection was the primary cause of death at 100 days for SCT (9/20 patients) whereas for DCT, there were no infection-related deaths! TNC and CD34+ cell dose did not differ between engrafting and non-engrafting units, however, we found that the engrafting units had a lower absolute lymphocyte count (ALC) in 8/10 evaluable cases.
Conclusion: DCT is an effective approach to overcome the TNC dose-limiting therapeutic benefit of CB transplantation. Although 100-day post-transplant infection frequency remains high, deaths from infection are markedly reduced and OS is significantly improved in DCT recipients, however, additional studies are needed to define the mechanism. For DCT, the engrafting unit does not have a higher TNC or CD34 cell dose but paradoxically; a lower ALC dose may be predictive.
Using the NOD/SCID Mice Model of Human Erythroleukemia for Evaluating the Cytotoxicity Activity of CB-CIK/NK Cells Stimulated by K562-DCs Fusion Vaccines.
Authors: Li Yang , Huang Shaoliang , Fang Jianpei , Zhang Xuchao , Wei Jing , Huang Wenge , Wu Yanfeng 
Published: October 2019

Abstract
CD3+CD56+ cytokine-induced killer (CIK) cells are prospective effectors for adoptive immunotherapy, CIK/NK cells incubated with K562-dendritic cells (DCs) fusion vaccines have more higher cytotoxicity activity. In this study, the efficacy and the safety of application of cord blood (CB) derived CIK/NK cells stimulated by K562-dendritic cells (DCs) fusion vaccines were evaluated in vivo by the NOD/SCID mice model of human erythroleukemia (K562 line, CD13+). DCs and CIK/NK cells were inducted by combination of cytokines from CB MNCs, DCs were fused with inactivated K562 tumor line by PEG (mw1500). 5 days before the harvest of CIK/NK cells, 1×105 K562-DCs fusion vaccines were co-cultured with 1×106 CB-CIK/NK cells to prepare for the K562-DCs fusion vaccines stimulated CIK/NK cells. NOD/SCID mice divided into six groups, eight in one group. Mice in A,B and C groups were inoculated with 1×106 K562 cells by tail vein. 24 hours later, 1×107 K562-DCs fusion vaccines stimulated CIK/NK cells and 1×107 unstimulated CIK/NK cells were transfued into the mice of group A and B, respectively. Group D and E were K562-DCs fusion vaccines stimulated CIK/NK cells and no-stimulated CIK/NK cells control, transfued by 1×107 stimulated CIK/NK cells and 1×107 no-stimulated CIK/NK cells, respectively. Group F is a normal control that no any inoculation were taken. None of the NOD/SCID mice in group C that inoculated with 1×106 K562 cells survived longer than 39 days, hepatosplenomegalic mass was seen in five mice. Death in group A and B were only one and two, respectively, at day 65 and day 56, 62. There was no tumour mass can be seen in group A and B, and the survial were more than 70 days. Both survival time of group A(69.38±1.77 days) and B(67.25±5.34 days) were longer than that of group C(30.38±4.57 days) significantly (P<0.01). The tumor marker (CD13) in periperal blood, live and lung of CIK/NK cells treated NOD/SCID mice (group A and B) significantly less than group C(P<0.01). There was no difference of CD56 positive in periperal blood of group A and B survival mice between that of the control (group D and E). These result indicated that K562-DCs fusion vaccines stimulating CB-CIK/NK cells have a potent anti-tumour activity in vivo and without any side-effect.
Reduced Toxicity Condition, Mixed Chimerism and Donor Stem Cells Infusion — A More Effective and Safely Model of Nonmyeloablative Allogeneic Stem Cell Transplantation (Seventy-Two Cases Report).
Authors: Ai Hui-Sheng , Guo Mei , Yu Chang-Lin , Wang Dan-Hong , Qiao Jian-Hui , Sun Qi-Yun , Sun Wan-Jun , Shi Zhang 
Published: October 2019

Abstract
Background Recently, the development of nonmyeloablative allogeneic stem cell transplantation (NST) which are associated with lower toxicity and mixed chimerism has improved the survival of old and young patients with haematology diseases. Otherwise, donor lymphocyte infusion (DLI) that is associated with high immunological activity and more graft versus leukaemia effect has also improved the complete remission rate of relapsed patients after transplant. But there are remain of some problems to have resolved which includes how to prevent from graft-versus-hostdisease (GVHD) and leukaemia relapsed after NST. We conducted A more effective and safely model of nonmyeloablative allogeneic stem cell transplantation which haved successfully been used in the seventy-two cases of haematology diseases.
Methods Seventy-two parients (year range 17–61) with HLA-march donor in acute leukaemia(n=33), chromic leukaemia (n=23) and MDS or SAA(n=16) were received reduced toxicity condition (cyclophosphamide, fludarabine, anti-thymocyte gloubin and cytarabine or busulfan) following a allogenic perpheral blood stem cell transplantation. GVHD prophylaxis consisted of cyclosporine A and Mycophenolate mofetil (MMF) for 90 days. All cases who has no aGVHD were received the donor frozen mobilization and apheresis perpheral blood stem cells(DSI) in 35 to 55 days after NST.
Results All Seventy-two patients passed smoothly the hematopoietic suppression stage and achieved engraftment of the donor cells which included 42 cases of full donor chimerism FDC), 30 cases of mixed chimerism (MC) in which 27 cases converted to FDC in 1–16 monthes and 3 cases developed graft rejection. Among the all of Seventy-two cases, the incidence of aGVHD (grade I–II=18, and grade III–IV=3) was 29.2% (n=21) in which 5 cases of aGVHD was caused by the DSI and stopped CSA and MMF. There are much higher rate aGVHD in the FDC group (n=15) than the MC group (n=6) The incidence of cGVHD was 30.6% (n=22). Among the 33 cases of acute leukaemia patients, five cases died from leukaemia relapsed (15.2%). Follow-up 3 to 75 months, survive rate of patients is 77.8% (n=56) and the 3 year estimated disease-free survival is 41.7%.
Conclusions These results shown that new protocol of NST is a much more effective and safty strategy for haematology patients, the use of conditions with CTX, Flud, ATG, Ara-C/BU reduced toxicity of transplant, the mixed chimerism help to prevent from the aGVHD, use of DSI both improved the MC converted to FDC and GVL effect but only slightly GVHD and no hypocellular which is much better than the DLI.
Efficacy and Safety of Using G-CSF on Day before Stem Cell Infusion (Day -1) in Hematopoietic Stem Cell Transplantation (HSCT) -A Single Institution Experience from India.
Authors: Sastry P.S.R.K. , Narayanan Prasad , Khadwal Alka , Biswas Ghansyam , Bhagwat Roshni , Bakshi Ashish , Parikh Purvish 
Published: October 2019

Abstract
Background: It is well established that recombinant human G-CSF accelerates neutrophil recovery following hematopoietic stem cell transplantation. However, the optimal timing of G-CSF following transplantation remains unknown. We have done a Phase II non randomized open label study on effects of adding an extra dose of G-CSF (filgrastim 5μgm/kg) on Day -1 of HSCT.
Patients and methods: Thirty nine consecutive patients who underwent HSCT in one year period were given G-CSF on Day -1(Day before stem cell infusion) in addition to the regular doses from Day +1 till engraftment.
Results: Among the 39, males were 31 and females 8 with 15 allograft and 24 autografts. The type of harvest was PBSC in 35, BM alone in 1and both in 3 cases. Disease wise distribution was AML-11, MM-8, NHL-6, HL-5, CML-4, MDS-2 and Aplastic Anemia, ALL and Ca nasopharynx 1 each. The median MNC and CD 34 doses infused were 5.4X108/Kg and 2.26X106/Kg respectively. Median days of Grade IV neutropenia was 11 (range 5–19) and that of ANC< 100 was 6 (range 2–19). Neutropenic fever was present for a median of 10 days (range 4–19). Neutrophil engraftment and platelet engraftment occurred at Day +11(range 8–13) and Day +21(range 11–73) respectively. Median number of packed cells and platelets (SDP) transfused were 4 and 5 respectively. Mucositis was present for a median of 9 days with Grade III in 51% (n=20) and Grade IV in 23% (n=9) patients. TPN was used in 76% (n=30) patients for a median days of 6 days. Median number of days of antibiotics use was 10 and 57% (n=22) needed 3 lines of antibiotics. Antifungals were used in 57% (n=22) and 95% of use was empirical. Infections were documented in 42% (n=16). Median days of hospitalization was 22 (range 13–38). Transplant related mortality was 10% (2 Auto and 2 Allo). After a median follow up of 113 days 79.71% (n=34) patients are alive with 71% (n=28) in complete remission. One patient with Ca nasopharynx had progressive disease on evaluation and one patient with peripheral T cell lymphoma developed a secondary leukemia (myeloid) post transplant.
Conclusions: Addition of G-CSF on Day -1 of HSCT is safe and provides stable engraftment and acceptable results in terms of neutropenic fever, requirement of blood products, antibiotics, TPN and duration of hospital stay. It needs to be compared in randomized trials with use of G-CSF from Day +1 onwards to prove its superiority over that schedule.