scholarly journals mRNA-Enhanced Cell Therapy and Cardiovascular Regeneration

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 187
Author(s):  
Palas K. Chanda ◽  
Roman Sukhovershin ◽  
John P. Cooke
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Cancer Immunotherapy ◽  
Vaccine Development ◽  
Drug Molecule ◽  
Therapeutic Modalities ◽  
Naturally Occurring ◽  
Cardiovascular Regeneration ◽  
Recent Advancement

mRNA has emerged as an important biomolecule in the global call for the development of therapies during the COVID-19 pandemic. Synthetic in vitro-transcribed (IVT) mRNA can be engineered to mimic naturally occurring mRNA and can be used as a tool to target “undruggable” diseases. Recent advancement in the field of RNA therapeutics have addressed the challenges inherent to this drug molecule and this approach is now being applied to several therapeutic modalities, from cancer immunotherapy to vaccine development. In this review, we discussed the use of mRNA for stem cell generation or enhancement for the purpose of cardiovascular regeneration.

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.

Abstract P011: Endothelial Differentiation and Lineage Tracing in Adipocyte-Derived Multipotent Cells

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Medet Jumabay ◽  
Raushan Abdmaulen ◽  
Yucheng Yao ◽  
Kristina Bostrom
Keyword(s):  
Stem Cell ◽  
Lineage Tracing ◽  
Collagen Gels ◽  
Cellular Origin ◽  
Differentiated Cells ◽  
Stem Cell Source ◽  
Cardiovascular Regeneration ◽  
Morphogenetic Protein ◽  
Dfat Cells

We previously showed that so-called de-differentiated fat (DFAT) cells, which are derived from mature white adipocytes, spontaneously differentiate into beating cardiomyocytes. Our aim in this study was to investigate if DFAT cells also differentiate into endothelial cells (ECs) in vitro, and to further examine the cellular origin of DFAT cells as well as adipose stromal cells (ASCs) using lineage tracing. First, we examined DFAT and ASCs prepared from aP2-Cre+/+;LacZ ROSA(R26R)+/+ double transgenic mice, which express LacZ under the aP2 promoter. The results revealed that 99.9% of DFAT cells and 45% of the ASCs stained positive for LacZ, supporting that the DFAT cells and part of the ASCs are of adipocytic origin. Second, we allowed newly isolated DFAT cells to spontaneously undergo EC differentiation, which was monitored by expression of EC lineage markers as determined by real-time PCR, immunofluorescence, and FACS. Expression of the EC markers CD31 and VE-cadherin increased progressively during 2 weeks in culture, the percentage of CD31(+) cells increased from 0.0% to 8.3%, and the cells formed multi-cellular tube structures when placed in Matrigel™/Collagen gels. The data supported that a fraction of the DFAT cells differentiate into ECs. Furthermore, the EC differentiation could be enhanced in DFAT cells by treatment with bone morphogenetic protein (BMP)-4 and BMP-9. In addition to EC differentiation, the DFAT cells also expressed markers of other cardiovascular lineages including smooth muscle cells and pericytes. The multipotency of DFAT cells suggests that cellular de-differentiation might be a way for differentiated cells to regain stem cell-like properties. Thus, white mature adipocytes maybe a new stem cell source for cardiovascular regeneration.

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 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 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.

In vitro study of SDF-1α-loaded injectable and thermally responsive hydrogels for adipose stem cell therapy by SDF-1/CXCR4 axis

2020 ◽  
Vol 8 (45) ◽  
pp. 10360-10372
Author(s):  
Siaka Fadera ◽  
Nai-Chen Cheng ◽  
Tai-Horng Young ◽  
I-Chi Lee
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
In Vitro Study ◽  
Adipose Stem Cell ◽  
Thermally Responsive ◽  
Ischemic Diseases ◽  
Responsive Hydrogels ◽  
Cxcr4 Axis

Thermoresponsive and injectable CS/βGP/HA hydrogels may provide an alternative for treating ischemic diseases via SDF-1/CXCR4 axis for ASC recruitment and retention.

A Phase II Study of Sequential Administration of DLI and Cytokine Induced Killer (CIK) Cells in Patients with Hematologic Malignancies Relapsing After Allogeneic Hematopoietic Stem Cell Transplantation: Preliminary Results

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 657-657
Author(s):  
Martino Introna ◽  
Alessandra Algarotti ◽  
Caterina Micò ◽  
Anna Grassi ◽  
Alice Pievani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Acute Gvhd ◽  
Hematologic Malignancies ◽  
Hematopoietic Stem ◽  
Cik Cells ◽  
Therapy Program ◽  
Sequential Administration ◽  
Dose Escalating

Abstract Abstract 657 Background: Cytokine Induced Killer (CIK) cells have been previously shown by us and others to possess non restricted, NK-like anti-tumoral cytotoxicity in vitro and in vivo, with little graft-versus host disease (GVHD), in vitro and in several animal models. We have previously performed a phase I study with donor derived CIK cells in 11 adult hematologic patients and shown that the infusions of CIK cells (median 12.4 × 106/kg, range 7.2 to 87.4) were well tolerated and no acute or late infusion related reactions were recorded. Acute GVHD (grade I and II) was observed in 4 patients and progressed into extensive chronic GVHD in two cases (Introna et al, Haematologica 92:952, 2007). Methods: This study is an open-labeled, multicenter, exploratory phase IIA study to evaluate the safety (dose-finding) and efficacy of a sequential administration of donor derived unmanipulated lymphocytes (DLI) plus in vitro expanded CIK cells to patients with hematologic malignancies relapsing after related or unrelated allogeneic hematopoietic stem cells transplantation. The protocol was formally approved by the italian competent national authority (Agenzia Italiana del Farmaco, AIFA) on 14/04/2009. Two infusions of unmanipulated DLI (1×106/kg each) were given with a minimum interval of 3 weeks. Three infusions of donor CIK cells were then administered according to a dose escalating program, starting 3 weeks after the second DLI. CIK administrations were separated by 3 weeks intervals. Up to 4 combinations of dose escalating levels were provided in sequential order until the maximal tolerated dose (MTD) was reached. Indeed the first triplet of patients was supposed to receive CIK cells at the doses of 1×106/kg, 1×106/kg and 5×106/kg, the second 1×106/kg, 5×106/kg, 5×106/kg, the third 1×106/kg, 5×106/kg,10×106/kg, the last triplet 5×106/kg, 5×106/kg, 10×106/kg. In case of grade II or more severe acute GVHD, the next scheduled infusion was planned to be suspended. Only grade IV acute GVHD was considered the dose limiting toxicity (DLT). Once identified the MTD, this same dose will be administered up to 24 patients in a two-stage Simon's design. Results: So far 16 patients have been enrolled and 12 are evaluable. No DLT (grade IV acute GVHD) was observed at any dose. One patient suffered from grade III skin and gut acute GVHD in the group which received the highest dose and the therapy was stopped after the first administration of CIK cells (5×106/kg), while another patient showed grade I skin acute GVHD in this same group, but completed the 3 administrations program. So far, 7 patients have received the highest dose of CIK cells and they all completed the schedule without toxicity except one case. As per protocol, the best clinical response was evaluated 100 days after the end of the last CIK administration. We observed 3 CR (3 AML), 5 PR (3 AML, 1 MM and 1 HD) and 4 NR (2 AML, 1 NHL and 1 MM) in the 12 evaluable patients. Of the 12 evaluable patients, 5 required additional therapy at the end of the cell therapy program because of NR (3 patients) or to improve the PR (2 patients). Four patients died after a mean 63 days (3 due to relapse and 1 for infection), 6 patients are in PR and 2 patients remain in CR. Conclusions: These preliminary observations suggest that the sequential infusion of DLI and CIK cells is feasible with relatively minor toxicity, the MTD has not been achieved and the triplet of three CIK administrations of 5×106/kg, 5×106/kg and 10×106/kg will be further evaluated in 17 additional patients. This cell therapy program confirms the antineoplastic activity of this cell therapy schedule in some patients relapsing after allogeneic stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

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