scholarly journals Electro-Acupuncture Promotes Endogenous Multipotential Mesenchymal Stem Cell Mobilization into the Peripheral Blood

2016 ◽  
Vol 38 (4) ◽  
pp. 1605-1617 ◽  
Author(s):  
Lizhen Liu ◽  
Qin Yu ◽  
Kaimin Hu ◽  
Binsheng Wang ◽  
Yiran Zhang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Peripheral Blood ◽  
Control Groups ◽  
Adult Rats ◽  
Differentiation Potential ◽  
Lineage Differentiation ◽  
Stromal Cell Derived Factor ◽  
Cell Mobilization

Background/Aims: Mobilization of endogenous stem cells is an appealing strategy for cell therapy However, there is little evidence for reproducible, effective methods of mesenchymal stem cell (MSC) mobilization. In the present study, we investigated the mobilizing effect of electro-acupuncture (EA) on endogenous MSCs. Methods: Normal adult rats were randomly divided into six groups, namely, EA for 14 days (EA14d), sham EA14d, EA21d, sham EA21d and matched control groups. MSC mobilization efficiency was determined by colony-forming unit fibroblast (CFU-F) assays. Mobilized peripheral blood (PB)-derived MSCs were identified by immunophenotype and multi-lineage differentiation potential. Results: CFU-F frequency was significantly increased in the PB of EA14d rats compared with the sham EA and control groups. Moreover, the number of CFU-Fs was increased further in the EA21d group. MSCs derived from EA-mobilized PB were positive for CD90 and CD44, but negative for CD45. Additionally, these cells could differentiate into adipocytes, osteoblasts, chondrocytes and neural-like cells in vitro. Finally, stromal cell-derived factor-1α (SDF-1α) was increased in the PB of rats subjected to EA, and the migration of MSCs was improved in response to SDF-1α. Conclusions: MSCs with multi-lineage differentiation potential can be mobilized by EA. Our data provide a promising strategy for MSC mobilization.

scholarly journals Isolation and Characterization of a Human Fetal Mesenchymal Stem Cell Population: Exploring the Potential for Cell Banking in Wound Healing Therapies

2019 ◽  
Vol 28 (11) ◽  
pp. 1404-1419
Author(s):  
Roger Esteban-Vives ◽  
Jenny Ziembicki ◽  
Myung Sun Choi ◽  
R. L. Thompson ◽  
Eva Schmelzer ◽  
...  
Keyword(s):  
Wound Healing ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Dermal Fibroblasts ◽  
Stem Cell Population ◽  
Differentiation Potential ◽  
Isolation And Characterization ◽  
Cell Banking ◽  
Lineage Stability

Various cell-based therapies are in development to address chronic and acute skin wound healing, for example for burns and trauma patients. An off-the-shelf source of allogeneic dermal cells could be beneficial for innovative therapies accelerating the healing in extensive wounds where the availability of a patient’s own cells is limited. Human fetal-derived dermal fibroblasts (hFDFs) show high in vitro division rates, exhibit low immunological rejection properties, and present scarless wound healing in the fetus, and previous studies on human fetal tissue-derived cell therapies have shown promising results on tissue repair. However, little is known about cell lineage stability and cell differentiation during the cell expansion process, required for any potential therapeutic use. We describe an isolation method, characterize a population, and investigate its potential for cell banking and thus suitability as a potential product for cell grafting therapies. Our results show hFDFs and a bone marrow-derived mesenchymal stem cell (BM-MSC) line shared identification markers and in vitro multilineage differentiation potential into osteogenic, chondrogenic, and adipogenic lineages. The hFDF population exhibited similar cell characteristics as BM-MSCs while producing lower pro-inflammatory cytokine IL-6 levels and higher levels of the wound healing factor hepatocyte growth factor. We demonstrate in vitro differentiation of hFDFs, which may be a problem in maintaining long-term lineage stability, potentially limiting their use for cell banking and therapy development.

Stromal Cell-Derived Factor (SDF-1) Mediates Stem Cell Mobilization and Homing to the Kidney after Acute Renal Failure.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2678-2678
Author(s):  
Florian E. Toegel ◽  
Jorge Isaac ◽  
Zhuma Hu ◽  
Kathy Weiss ◽  
Christof Westenfelder
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Stem Cell ◽  
Atp Depletion ◽  
Blood Levels ◽  
Hematopoietic Stem ◽  
Organ Repair ◽  
Stromal Cell Derived Factor ◽  
Cell Mobilization

Abstract The chemokine stromal cll-derived factor-1 (SDF-1) and its receptor CXCR4, expressed by hematopoietic stem cells (HSC) and other cells, represents a major mediator-system for G-CSF-induced hematopoietic stem cell (HSC) mobilization and stem cell (SC) homing to the bone marrow (BM) after BM transplantation. HSC have been shown to contribute to repair processes in kidneys damaged by ischemia and HSC as well as endothelial progenitor cells (EPC) are mobilized in response to kidney damage. The signals mediating this process are currently unknown. We tested the hypothesis that SDF-1 mediates both mobilization and homing of SCs into the kidney with acute renal failure (ARF) and may thus be crucial to SC-mediated organ repair. SDF-1 is expressed in normal kidneys and upregulated in ischemically injured (60 min bi- or unilateral renal pedicle clamp) mouse kidneys (FVB strain) as evaluated by immunohistochemistry, in-situ hybridization, quantitative RT-PCR and ELISA. Post ARF SDF-1 was upregulated in sublethally injured proximal tubular cells (PTC), peripheral blood levels of SDF-1 rose, and circulating CD34+ and Colony-forming Units of Cell numbers as well as EPCs increased significantly. In vitro chemotaxis of SC from the top of transwell inserts towards the bottom well, containing cultured PTC that exhibited augmented SDF-1 expression post partial ATP depletion, increased significantly, a response that was abolished when SC cells were preincubated with CXCR4 antibody. Injected, CFDA-labeled, BM cells were only recruited to ischemic kidneys (bi- or unilateral), a response that was also blocked after SC pre-incubation with CXCR4 antibody. Our data show that there is increased renal SDF-1 expression after ARF and secretion into the circulation, which, in turn, stimulates HSC and EPC-mobilization into the circulation and directs homing into the post-ischemic kidney. Therefore, both circulating and administered SC and other CXCR4-expressing cells can be recruited to the injured kidney, where they, as we showed previously, are able to greatly support effective tissue repair, functional recovery and animal survival following ARF.

Differential Role for VLA-5 in Mobilization of Heamotopoieic Stem Cells Toward Peripheral Blood and Homing to Bone Marrow and Spleen.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2190-2190 ◽  
Author(s):  
Pieter K. Wierenga ◽  
Ellen Weersing ◽  
Bert Dontje ◽  
Gerald de Haan ◽  
Ronald P. van Os
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Hematopoietic Stem ◽  
Late Antigen ◽  
Cell Mobilization

Abstract Adhesion molecules have been implicated in the interactions of hematopoietic stem and progenitor cells with the bone marrow extracellular matrix and stromal cells. In this study we examined the role of very late antigen-5 (VLA-5) in the process of stem cell mobilization and homing after stem cell transplantation. In normal bone marrow (BM) from CBA/H mice 79±3 % of the cells in the lineage negative fraction express VLA-5. After mobilization with cyclophosphamide/G-CSF, the number of VLA-5 expressing cells in mobilized peripheral blood cells (MPB) decreases to 36±4%. The lineage negative fraction of MPB cells migrating in vitro towards SDF-1α (M-MPB) demonstrated a further decrease to 3±1% of VLA-5 expressing cells. These data are suggestive for a downregulation of VLA-5 on hematopoietic cells during mobilization. Next, MPB cells were labelled with PKH67-GL and transplanted in lethally irradiated recipients. Three hours after transplantation an increase in VLA-5 expressing cells was observed which remained stable until 24 hours post-transplant. When MPB cells were used the percentage PKH-67GL+ Lin− VLA-5+ cells increased from 36% to 88±4%. In the case of M-MPB cells the number increased from 3% to 33±5%. Although the increase might implicate an upregulation of VLA-5, we could not exclude selective homing of VLA-5+ cells as a possible explanation. Moreover, we determined the percentage of VLA-5 expressing cells immediately after transplantation in the peripheral blood of the recipients and were not able to observe any increase in VLA-5+ cells in the first three hours post-tranpslant. Finally, we separated the MPB cells in VLA-5+ and VLA-5− cells and plated these cells out in clonogenic assays for progenitor (CFU-GM) and stem cells (CAFC-day35). It could be demonstared that 98.8±0.5% of the progenitor cells and 99.4±0.7% of the stem cells were present in the VLA-5+ fraction. Hence, VLA-5 is not downregulated during the process of mobilization and the observed increase in VLA-5 expressing cells after transplantation is indeed caused by selective homing of VLA-5+ cells. To shed more light on the role of VLA-5 in the process of homing, BM and MPB cells were treated with an antibody to VLA-5. After VLA-5 blocking of MPB cells an inhibition of 59±7% in the homing of progenitor cells in bone marrow could be found, whereas homing of these subsets in the spleen of the recipients was only inhibited by 11±4%. For BM cells an inhibition of 60±12% in the bone marrow was observed. Homing of BM cells in the spleen was not affected at all after VLA-5 blocking. Based on these data we conclude that mobilization of hematopoietic progenitor/stem cells does not coincide with a downregulation of VLA-5. The observed increase in VLA-5 expressing cells after transplantation is caused by preferential homing of VLA-5+ cells. Homing of progenitor/stem cells to the bone marrow after transplantation apparantly requires adhesion interactions that can be inhibited by blocking VLA-5 expression. Homing to the spleen seems to be independent of VLA-5 expression. These data are indicative for different adhesive pathways in the process of homing to bone marrow or spleen.

scholarly journals The Osteogenic Capacity of HumanAmniotic Membrane Mesenchymal Stem Cell (hAMSC) and Potential for Application in Maxillofacial Bone Reconstruction in Vitro Study

2020 ◽  
Vol 4 (1) ◽  
pp. 17
Author(s):  
David Kamadjaja
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Osteogenic Differentiation ◽  
Amniotic Membrane ◽  
Isolation Procedure ◽  
Target Cells ◽  
Human Amniotic Membrane ◽  
Bone Reconstruction ◽  
Differentiation Potential

Amniotic membrane of human placenta is a source of abundant mesenchymal stem cell (hAMSC) which makes it a potential source of allogeneic multipotent cell for bone healing.  However, much has to be explored about its isolation procedure and the osteogenic differentiation potential. The aims of this study are to establish the procurement procedure of human amniotic membrane, the isolation   and culture   of hAMSC, the MSC phenotypic characterization, and the in vitro osteogenic differentiation of hAMSC.  Results of the study are as follows. The quality of human amniotic membrane would be best if procured from Caesarean operation under highly aseptic condition to avoid fungal and bacterial contamination on the culture.  Isolation procedure using modified   Soncini protocol yielded large amount of MSC with high proliferative capacity in culture medium.  Characterization of hAMSC showed that the majority of the target cells exhibited specific MSC markers (CD10S and CD90) with a small number of these cells expressing CD45the marker of hematopoeitic cells. The in vitro osteogenic differentiation of hAMSC  followed by Alizarin  Red staining showed that  osteoblastic differentiation  was  detected in a significantly   high  number  of cells.  This study concludes that hAMSCs isolated from human amniotic membrane have the capacity for in vitro osteogenesis which makes them be one of the potential allogeneic stem cells for application in maxillofacial bone reconstruction.

CD34+ Subclasses of Blood Stem Cell Grafts Collected After Plerixafor Injection in Non-Hodgkin Lymphoma (NHL) Patients Mobilizing Poorly with Chemotherapy Plus G-CSF

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2990-2990
Author(s):  
Esa Jantunen ◽  
Ville Varmavuo ◽  
Piia Valonen ◽  
Taru Kuittinen ◽  
Tapio Nousiainen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
In Vitro Growth ◽  
Control Groups ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 2990 Background: Mobilization of blood stem cells is difficult in a subgroup of patients with standard methods. Plerixafor, a CXCR4 antagonist, has been used for stem cell mobilization in combination with G-CSF for some years. Mobilization method used may affect not only efficacy of stem cell mobilization and collection but also graft content which on the other hand may have effect on post-transplant outcomes. No data is available on CD34+ subclasses in grafts collected after plerixafor administration in patients who mobilize poorly with chemotherapy plus G-CSF. Patients and Methods: Altogether blood stem cell grafts collected from 26 NHL patients were studies. Thirteen patients (8 M, 5 F, median age 51 yrs) were mobilized with a combination of chemotherapy and G-CSF ad received plerixafor due to poor mobilization followed by stem cell apheressis. Thirteen patients (10 M, 3 F, median age 56 yrs) were mobilized with chemotherapy plus G-CSF without plerixafor and served as controls. Samples from the first collection after plerixafor and from the first apheresis of control patients were studied by flow cytometry using the following antibodies: CD34, CD38, CD 117, CD133, CD19 and CD45. Viability of CD34+ cells after freezing was assessed with 7-aminoactinomycin D staining. Also in vitro growth of granulocyte/macrophage progenitors (GM-CFU) were assessed from all grafts. Patients were followed after high-dose chemotherapy in regard to hematopoietic reconstitution. Results: The number of viable cells in the grafts was comparable between the plerixafor and the control groups (Table 1). The number of the most primitive stem cells (CD34+CD38−CD133+) was higher in plerixafor mobilized grafts (Table 1). Most of the CD34+ cells were myeloid progenitors, as defined by their CD117 antigen co-expression. No differences in GM-CFU were observed between the groups. All except one patient had received high-dose therapy. The median number of CD34+ cells collected from the patients was comparable (3.1 vs. 3.3 × 106/kg). The median time to reach neutrophils > 10 × 109/L was 10 days from the stem cell infusion in both groups and time to unsupported platelets was also comparable (16 d vs. 13 d). Platelet counts at 1 month, 3 months and 6 months were comparable between the groups. Absolute lymphocyte counts were higher in plerixafor group but the differences were not statistically significant. One early toxic death occurred in the plerixafor mobilized group and one death due to disease recurrence in both groups with a median follow-up of 301 and 348 days from stem cell infusion in prelixafor and control groups, respectively. Conclusions: Plerixafor added to chemomobilization in NHL patients resulted in higher number of the most primitive CD34+ cells in the graft with comparable in vitro growth and engraftment potential after BEAM chemotherapy when compared to patients mobilized without plerixafor. Longer follow-up of higher patient numbers are needed to evaluate whether differences in graft content have an effect on patient outcomes. Disclosures: Jantunen: Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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