Abstract 8: Transplantation of Mouse Adipose Derived Stem Cell Sheet into Infarcted Rat Myocardium Increase Cell Engraftment and Cardiac Function

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Jong-Ho Kim ◽  
Hyung Joon Joo ◽  
Ha-Rim Seo ◽  
Long-Hui Cui ◽  
Mi-Na Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Cell Sheet ◽  
The Other ◽  
Differentiation Potential ◽  
Significance Level ◽  
Infarct Region ◽  
Cell Engraftment ◽  
Cell Proliferation And Differentiation

Background: Cell sheet technology has magnified as an important transplantation skill. Mouse adipose derived stem cells (mADSCs) can secrete various growth factors, which promote the repair of damaged cardiomyocyte and protecting cells from death. In addition, autologous cell source to easily obtain from patients are promising candidates for cell therapy in cardiovascular field. Methods: mADSCs were confirmed stem cell properties and secreted cytokines were evaluated in vitro. Eighteen acute myocardial infarction (AMI) rats were divide into 3 group; sham (n=6), suspended mADSCs (n=6), and mADSCs sheet (n=6) groups. In the mADSCs sheet group, 60х106 cells were cultured for 2 days onto temperature-responsive polymers and the sheets were then transplanted over the infarct region. In additional, the sheet was made of carboxyfluorescein diacetate succinimidyl ester (CFDA) -labelled mADSCs to confirmed cell survival. Engraftment and differentiation were blindly assessed after 28 days. Results: The mADSCs expressed Sca-1+ and represented multi-differentiation potential. Interestingly, EGF and IGF levels significantly increased in the mADSCs sheet. Significant improvements in ejection fraction and fraction shortening value were observed in the mADSCs sheet and suspended mADSCs groups compared with the sham group at 14 and 28 days. But, it was not higher significance level in the mADSCs sheet group than in the suspended mADSCs group. Engraftment range and fibrosis area of infarct region were significantly higher in the mADSCs sheet group compared to the other two groups at 4, 14 and 28 days. In significant expressed cytokines (bFGF, IL-1a, IL-1ra, CT-1, EGF, TGFb1, IGF-1, IGF-2 and MCP-1) were observed in the mADSCs sheet group compared with the other 2 groups at 28 days after transplantation. In addition, in the mADSCs sheet was confirmed endothelial differentiation by Von Willebrand factor (vWF) at 4, 14 and 28 days. Conclusions: Transplantation of mADSCs sheet into rat infarcted myocardium increased engraftment and survival of transplanted cells. The mADSCs sheet is very useful for the study of stem cell proliferation and differentiation as well as for cell therapy in cardiovascular field.

scholarly journals Cell Source-Dependent In Vitro Chondrogenic Differentiation Potential of Mesenchymal Stem Cell Established from Bone Marrow and Synovial Fluid of Camelus dromedarius

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1918
Author(s):  
Young-Bum Son ◽  
Yeon Ik Jeong ◽  
Yeon Woo Jeong ◽  
Mohammad Shamim Hossein ◽  
Per Olof Olsson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Synovial Fluid ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Chondrocyte Differentiation ◽  
Differentiation Potential ◽  
Proliferation Capacity

Mesenchymal stem cells (MSCs) are promising multipotent cells with applications for cartilage tissue regeneration in stem cell-based therapies. In cartilage regeneration, both bone marrow (BM-MSCs) and synovial fluid (SF-MSCs) are valuable sources. However, the cellular characteristics and chondrocyte differentiation potential were not reported in either of the camel stem cells. The in vitro chondrocyte differentiation competence of MSCs, from (BM and SF) sources of the same Camelus dromedaries (camel) donor, was determined. Both MSCs were evaluated on pluripotent markers and proliferation capacity. After passage three, both MSCs showed fibroblast-like morphology. The proliferation capacity was significantly increased in SF-MSCs compared to BM-MSCs. Furthermore, SF-MSCs showed an enhanced expression of transcription factors than BM-MSCs. SF-MSCs exhibited lower differentiation potential toward adipocytes than BM-MSCs. However, the osteoblast differentiation potential was similar in MSCs from both sources. Chondrogenic pellets obtained from SF-MSCs revealed higher levels of chondrocyte-specific markers than those from BM-MSCs. Additionally, glycosaminoglycan (GAG) content was elevated in SF-MSCs related to BM-MSCs. This is, to our knowledge, the first study to establish BM-MSCs and SF-MSCs from the same donor and to demonstrate in vitro differentiation potential into chondrocytes in camels.

scholarly journals Non-Ionizing Radiation for Cardiac Human Amniotic Mesenchymal Stromal Cell Commitment: A Physical Strategy in Regenerative Medicine

2018 ◽  
Vol 19 (8) ◽  
pp. 2324 ◽  
Author(s):  
Mario Ledda ◽  
Enrico D’Emilia ◽  
Maria Lolli ◽  
Rodolfo Marchese ◽  
Claudio De Lazzari ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Adult Stem Cells ◽  
Myocardial Damage ◽  
Stem Cell Differentiation ◽  
Differentiation Markers ◽  
Innovative Strategy ◽  
Cell Commitment

Cell therapy is an innovative strategy for tissue repair, since adult stem cells could have limited regenerative ability as in the case of myocardial damage. This leads to a local contractile dysfunction due to scar formation. For these reasons, refining strategy approaches for “in vitro” stem cell commitment, preparatory to the “in vivo” stem cell differentiation, is imperative. In this work, we isolated and characterized at molecular and cellular level, human Amniotic Mesenchymal Stromal Cells (hAMSCs) and exposed them to a physical Extremely Low Frequency Electromagnetic Field (ELF-EMF) stimulus and to a chemical Nitric Oxide treatment. Physically exposed cells showed a decrease of cell proliferation and no change in metabolic activity, cell vitality and apoptotic rate. An increase in the mRNA expression of cardiac and angiogenic differentiation markers, confirmed at the translational level, was also highlighted in exposed cells. Our data, for the first time, provide evidence that physical ELF-EMF stimulus (7 Hz, 2.5 µT), similarly to the chemical treatment, is able to trigger hAMSC cardiac commitment. More importantly, we also observed that only the physical stimulus is able to induce both types of commitments contemporarily (cardiac and angiogenic), suggesting its potential use to obtain a better regenerative response in cell-therapy protocols.

Acoustic radiation force for vascular stem cell therapy: An in vitro validation

2011 ◽  
Author(s):  
Mehmet Kaya ◽  
Catalin Toma ◽  
Jianjun Wang ◽  
Michelle Grata ◽  
Huili Fu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Acoustic Radiation ◽  
Radiation Force ◽  
Acoustic Radiation Force

scholarly journals Liposomal Daunorubicin/Cytarabine As a Bridge to Donor Lymphocyte Infusion or Allogeneic Stem Cell Transplantation for High-Risk Acute Myelogenous Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5726-5726
Author(s):  
Daulath Singh ◽  
Patrick Hagen ◽  
Nasheed Hossain ◽  
Scott E. Smith ◽  
Patrick J. Stiff ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Cell Therapy ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Donor Lymphocyte Infusion ◽  
The Other ◽  
Myelogenous Leukemia ◽  
Liposomal Daunorubicin

Introduction: Liposomal daunorubicin/cytarabine (Vyxeos®) is a dual drug liposomal encapsulation of cytarabine and daunorubicin, delivering drugs at a fixed 5:1 synergistic ratio for a longer therapeutic period. Compared to standard 7+3, liposomal cytarabine/daunorubicin (lipo-cytara/dauno) patients had improved survival and remission rates in a pivotal phase III study of elder adults with high-risk acute myelogenous leukemia (AML). Furthermore, more lipo-cytara/dauno patients went to allogeneic stem cell transplantation (HCT), with lower mortality and improved survival compared to those induced with 7+3. With its enhanced pharmacokinetics, lipo-cytara/dauno may provide a potent bridge to transplant. We report our experience using lipo-cytara/dauno as a bridge to same donor lymphocyte infusion (DLI) or different donor HCT in high-risk AML. Methods: We retrospectively reviewed all patients who received lipo-cytara/dauno at our institution since the FDA approval in August 2017. Of the 21 patients who have been treated, 9 received it as a bridge to cell therapy. All patients received the drug by usual means under the FDA label. Results: The median age of the 9 patients who received lipo-cytara/dauno as a bridge to cell therapy was 59 years. Seven were male, and two were female. Patients had had 1-4 prior lines of chemotherapy (median 2) with 7 of 9 patients having received prior standard 7+3 induction (cytarabine 100-200 mg/m2 x 7 days infusion and daunorubicin 60-90 mg/m2 x 3 days). Most had adverse cytogenetics, and all 9 patients received full lipo-cytara/dauno induction (daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 on Days 1, 3, and 5) as outpatient therapy [Table]. Of the 9 patients, 6 had AML with very early relapse after HCT, with median time to relapse of 4 months (range 3 to 7 months). All 6 successfully proceeded to their planned cell infusion: 5 received same donor DLI after melphalan at 140 mg/m2, and 1 underwent second HCT from a different donor with busulfan/fludarabine conditioning at Days 15-40 after lipo-cytara/dauno. Of the remaining 3, two had relapsed AML after an initial remission (one was in first complete remission (CR1) for 3 months after 7+3/midostaurin induction and the other was in CR1 for 7 months after 7+3 induction/high dose cytarabine consolidation) and one had primary refractory disease (PREF) after 7+3 and azacitidine/venetoclax induction regimens. All 3 successfully underwent first HCT at Days 15-100 days after lipo-cytara/dauno bridge. The PREF patient received fludarabine/cyclophosphamide/TBI conditioning followed by matched unrelated donor transplant. Of the 2 with relapsed AML after initial remission, one received busulfan/fludarabine/thiotepa conditioning followed by umbilical cord stem cell transplantation and the other patient received fludarabine/cyclophosphamide/TBI conditioning prior to matched related donor transplant. Six of 9 had Day 14 bone marrow biopsies after lipo-cytara/dauno: 2 were in CR, 2 had >80% cytoreduction, and 2 had similar blast count. Three with persistent disease underwent reinduction with lipo-cytara/dauno (Days 1 and 3) and proceeded straight to cell therapy after. Median days to hospitalization after outpatient lipo-cytara/dauno was 6 days (range 3 to 14 days). Four out of 9 patients remain alive. Two were very early post HCT relapses (relapsed at 3 and 6 months post-HCT), both of which are remarkably in CR at 14 and 17 months after second cell therapy. Interestingly, both had CNS relapse, which were successfully treated, and both remain alive and in remission today. The other two had relapsed AML and PREF AML and underwent first HCT after lipo-cytara/dauno bridge. They remain alive and in remission at 1 and 8 months. Conclusion: In this retrospective study, outpatient lipo-cytara/dauno as a bridge to cell therapy is feasible and effective in very high-risk AML with no other viable options. While preliminary, survival appears favorable to that reported elsewhere at 14-23% at 1 year in this poor risk group, including those with adverse cytogenetic and/or very early post-HCT relapse. Prospective multi-center trials are planned to further evaluate lipo-cytara/dauno as a bridge to DLI/HCT in those with early relapse post-HCT and in those with refractory disease, with therapy to include CNS prophylaxis. Disclosures Stiff: Gilead/Kite Pharma: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Gamida-Cell: Research Funding; Incyte: Research Funding; Cellectar: Research Funding; Unum: Research Funding. Tsai:Jazz pharmaceuticals: Speakers Bureau; Jazz pharmaceuticals: Consultancy.

scholarly journals Positively Correlated CD47 Activation and Autophagy in Umbilical Cord Blood-Derived Mesenchymal Stem Cells during Senescence

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Gee-Hye Kim ◽  
Yun Kyung Bae ◽  
Ji Hye Kwon ◽  
Miyeon Kim ◽  
Soo Jin Choi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Growth ◽  
Cell Therapy ◽  
Critical Role ◽  
Therapeutic Effects ◽  
Stem Cell Maintenance ◽  
Selection Of

Autophagy plays a critical role in stem cell maintenance and is related to cell growth and cellular senescence. It is important to find a quality-control marker for predicting senescent cells. This study verified that CD47 could be a candidate to select efficient mesenchymal stem cells (MSCs) to enhance the therapeutic effects of stem cell therapy by analyzing the antibody surface array. CD47 expression was significantly decreased during the expansion of MSCs in vitro ( p < 0.01 ), with decreased CD47 expression correlated with accelerated senescence phenotype, which affected cell growth. UCB-MSCs transfected with CD47 siRNA significantly triggered the downregulation of pRB and upregulation of pp38, which are senescence-related markers. Additionally, autophagy-related markers, ATG5, ATG12, Beclin1, and LC3B, revealed significant downregulation with CD47 siRNA transfection. Furthermore, autophagy flux following treatment with an autophagy inducer, rapamycin, has shown that CD47 is a key player in autophagy and senescence to maintain and regulate the growth of MSCs, suggesting that CD47 may be a critical key marker for the selection of effective stem cells in cell therapy.

scholarly journals Human mesenchymal stem cell sheets in xeno-free media for possible allogenic applications

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kyungsook Kim ◽  
Sophia Bou-Ghannam ◽  
Hallie Thorp ◽  
David W. Grainger ◽  
Teruo Okano
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Subcutaneous Tissue ◽  
Cell Sheet ◽  
Human Mesenchymal Stem Cell ◽  
Human Umbilical Cord ◽  
Target Tissue ◽  
Post Transplantation ◽  
Allogeneic Cell ◽  
Allogeneic Cell Therapy

Abstract Cell-based therapies are increasingly focused on allogeneic stem cell sources because of several advantages in eliminating donor variability (e.g., aging and disease pathophysiology) affecting stem cell quality and in cell-banked sourcing of healthy donors to enable “off-the-shelf” products. However, allogeneic cell therapy is limited by host patient immunologic competence and inconsistent performance due to cell delivery methods. To address allogeneic cell therapy limitations, this study developed a new allogeneic stem cell sheet using human umbilical cord mesenchymal stem cells (hUC-MSC) that present low antigenicity (i.e., major histocompatibility complex, MHC). Optimal conditions including cell density, passage number, and culture time were examined to fabricate reliable hUC-MSC sheets. MHC II antigens correlated to alloimmune rejection were barely expressed in hUC-MSC sheets compared to other comparator MSC sheets (hBMSC and hADSC). hUC-MSC sheets easily graft spontaneously onto subcutaneous tissue in immune-deficient mice within 10 minutes of placement. No sutures are required to secure sheets to tissue because sheet extracellular matrix (ECM) actively facilitates cell-target tissue adhesion. At 10 days post-transplantation, hUC-MSC sheets remain on ectopic target tissue sites and exhibit new blood vessel formation. Furthermore, implanted hUC-MSC sheets secrete human HGF continuously to the murine target tissue. hUC-MSC sheets described here should provide new insights for improving allogenic cell-based therapies.

scholarly journals Stem Cells as a Resource for Treatment of Infertility-related Diseases

2019 ◽  
Vol 19 (8) ◽  
pp. 539-546
Author(s):  
Jing Wang ◽  
Chi Liu ◽  
Masayuki Fujino ◽  
Guoqing Tong ◽  
Qinxiu Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
In Vitro Fertilization ◽  
Cell Therapy ◽  
Reproductive Medicine ◽  
Intrauterine Insemination ◽  
Reproductive Age ◽  
Vitro Fertilization ◽  
Undifferentiated Cells

Worldwide, infertility affects 8-12% of couples of reproductive age and has become a common problem. There are many ways to treat infertility, including medication, intrauterine insemination, and in vitro fertilization. In recent years, stem-cell therapy has raised new hope in the field of reproductive disability management. Stem cells are self-renewing, self-replicating undifferentiated cells that are capable of producing specialized cells under appropriate conditions. They exist throughout a human’s embryo, fetal, and adult stages and can proliferate into different cells. While many issues remain to be addressed concerning stem cells, stem cells have undeniably opened up new ways to treat infertility. In this review, we describe past, present, and future strategies for the use of stem cells in reproductive medicine.

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.

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