Application of some graphene derivatives to increase the efficiency of stem cell therapy

Author(s):  
Tahereh Foroutan

: Graphene and its derivatives have application potential in many areas such as environmental technology, catalysis, biomedicine, and in particular, stem cell-based differentiation and regenerative therapies. Mesenchymal stem cell transplantation has emerged as a potential therapy for some diseases, such as acute kidney damage, liver failure and myocardial infarction. However, the poor survival of transplanted stem cells in such applications has significantly limited their therapeutic effectiveness. Graphene-based materials can improve the therapeutic efficacy of stem cells as they prevent the death of implanted cells by attaching them prior to implantation and increasing their paracrine secretion. In this review, we will highlight a number of recent studies that have investigated the potential use of graphene or its derivatives in stem cell applications and the prevention of transplanted stem cells from cell death, thereby improving their therapeutic efficacy.

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 86 ◽  
Author(s):  
Jung Hyun Shin ◽  
Chae-Min Ryu ◽  
Hyein Ju ◽  
Hwan Yeul Yu ◽  
Sujin Song ◽  
...  

The purpose of this study was to reduce the amount of stem cells used in treating preclinical interstitial cystitis (IC model) by investigating the synergistic effects of multipotent mesenchymal stem cells (M-MSCs; human embryonic stem cell-derived) and N-acetylcysteine (NAC). Eight-week-old female Sprague-Dawley rats were divided into seven groups, i.e., sham (n = 10), lipopolysaccharide/protamine sulfate (LPS/PS; n = 10), LPS/PS + NAC (n = 10), LPS/PS with 25K MSC (n = 10), LPS/PS with 50K MSC (n = 10) LPS/PS + 25K MSC + NAC (n = 10), and LPS/PS + 50K MSC + NAC (n = 10). To induce the IC rat model, protamine sulfate (10 mg, 45 min) and LPS (750 μg, 30 min) were instilled once a week for five consecutive weeks via a transurethral PE-50 catheter. Phosphate-buffered saline (PBS) was used in the sham group. One week after the final instillation, M-MSCs with two suboptimal dosages (i.e., 2.5 or 5.0 × 104 cells) were directly transplanted into the outer-layer of the bladder. Simultaneously, 200 mg/kg of NAC or PBS was intraperitoneally injected daily for five days. The therapeutic outcome was evaluated one week after M-MSC or PBS injection by awake cystometry and histological analysis. Functionally, LPS/PS insult led to irregular micturition, decreased intercontraction intervals, and decreased micturition volume. Both monotherapy and combination therapy significantly increased contraction intervals, increased urination volume, and reduced the residual volume, thereby improving the urination parameters compared to those of the LPS group. In particular, a combination of NAC dramatically reduced the amount of M-MSCs used for significant restoration in histological damage, including inflammation and apoptosis. Both M-MSCs and NAC-based therapy had a beneficial effect on improving voiding dysfunction, regenerating denudated urothelium, and relieving tissue inflammation in the LPS-induced IC/BPS rat model. The combination of M-MSC and NAC was superior to MSC or NAC monotherapy, with therapeutic efficacy that was comparable to that of previously optimized cell dosage (1000K) without compromised therapeutic efficacy.


2021 ◽  
pp. ASN.2021081073
Author(s):  
Melissa Little ◽  
Benjamin Humphreys

Fifteen years ago, this journal published a review outlining future options for regenerating the kidney. At that time, stem cell populations were being identified in multiple tissues, the concept of stem cell recruitment to a site of injury was of great interest, and the possibility of postnatal renal stem cells was growing in momentum. Since that time, we have seen the advent of human induced pluripotent stem cells, substantial advances in our capacity to both sequence and edit the genome, global and spatial transcriptional analysis down to the single-cell level, and a pandemic that has challenged our delivery of health care to all. This article will look back over this period of time to see how our view of kidney development, disease, repair, and regeneration has changed and envision a future for kidney regeneration and repair over the next 15 years.


Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 379
Author(s):  
Rabia Ikram ◽  
Shamsul Azlin Ahmad Shamsuddin ◽  
Badrul Mohamed Jan ◽  
Muhammad Abdul Qadir ◽  
George Kenanakis ◽  
...  

Thanks to stem cells’ capability to differentiate into multiple cell types, damaged human tissues and organs can be rapidly well-repaired. Therefore, their applicability in the emerging field of regenerative medicine can be further expanded, serving as a promising multifunctional tool for tissue engineering, treatments for various diseases, and other biomedical applications as well. However, the differentiation and survival of the stem cells into specific lineages is crucial to be exclusively controlled. In this frame, growth factors and chemical agents are utilized to stimulate and adjust proliferation and differentiation of the stem cells, although challenges related with degradation, side effects, and high cost should be overcome. Owing to their unique physicochemical and biological properties, graphene-based nanomaterials have been widely used as scaffolds to manipulate stem cell growth and differentiation potential. Herein, we provide the most recent research progress in mesenchymal stem cells (MSCs) growth, differentiation and function utilizing graphene derivatives as extracellular scaffolds. The interaction of graphene derivatives in human and rat MSCs has been also evaluated. Graphene-based nanomaterials are biocompatible, exhibiting a great potential applicability in stem-cell-mediated regenerative medicine as they may promote the behaviour control of the stem cells. Finally, the challenges, prospects and future trends in the field are discussed.


2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Mina Abedi ◽  
Sepideh Alavi-Moghadam ◽  
Moloud Payab ◽  
Parisa Goodarzi ◽  
Fereshteh Mohamadi-jahani ◽  
...  

AbstractSystemic sclerosis is a rare chronic autoimmune disease with extensive microvascular injury, damage of endothelial cells, activation of immune responses, and progression of tissue fibrosis in the skin and various internal organs. According to epidemiological data, women’s populations are more susceptible to systemic sclerosis than men. Until now, various therapeutic options are employed to manage the symptoms of the disease. Since stem cell-based treatments have developed as a novel approach to rescue from several autoimmune diseases, it seems that stem cells, especially mesenchymal stem cells as a powerful regenerative tool can also be advantageous for systemic sclerosis treatment via their remarkable properties including immunomodulatory and anti-fibrotic effects. Accordingly, we discuss the contemporary status and future perspectives of mesenchymal stem cell transplantation for systemic sclerosis.


2017 ◽  
Vol 4 (3-4) ◽  
pp. 234-235 ◽  
Author(s):  
Vlassov V Salval ◽  
Yone Moto

More than 500 clinical trials are using mesenchymal stem cells (MSCs) in the world to treat some different diseases. The safety of expanded MSC transplantation is the most important thing to ensure that this therapy can become the routine treatment for human diseases. More than five MSCs based stem cell drug products are approved at various countries demonstrated that expanded MSCs are safe in both local injection and transfusion. Moreover, some recent reports for 5 and 10 years followed-up clinical trials using expanded MSCs confirmed that there is not different tumorigenesis between the patients with and without expanded MSC transplantation. This letter aims to provide some evidences about the safety of expanded MSCs in clinical applications. However, the MSC quality should be stritcly controlled during the in vitro MSC expansion.


2020 ◽  
Vol 58 (5) ◽  
pp. 881-887
Author(s):  
Shuta Ishigami ◽  
Toshikazu Sano ◽  
Sunaya Krishnapura ◽  
Tatsuo Ito ◽  
Shunji Sano

Abstract Significant achievements in paediatric cardiology, surgical treatment and intensive care of congenital heart disease have drastically changed clinical outcomes for paediatric patients. Nevertheless, late-onset heart failure in children after staged surgeries still remains a serious concern in the medical community. Heart transplantation is an option for treatment; however, the shortage of available organs is a persistent problem in many developed countries. In order to resolve these issues, advanced technologies, such as innovative mechanical circulatory support devices and regenerative therapies, are strongly desired. Accumulated evidence regarding cell-based cardiac regenerative therapies has suggested their safety and efficacy in treating adult heart failure. Given that young children seem to have a higher regenerative capacity than adults, stem cell-based therapies appear a promising treatment option for paediatric heart failure as well. Based on the findings from past trials and studies, we present the potential of various different types of stem cells, ranging from bone marrow mononuclear cells to cardiosphere-derived stem cells for use in paediatric cell-based therapies. Here, we assess both the current challenges associated with cell-based therapies and novel strategies that may be implemented in the future to advance stem cell therapy in the paediatric population.


2018 ◽  
Vol 27 (9) ◽  
pp. 1313-1319 ◽  
Author(s):  
Chiao-Fang Teng ◽  
Long-Bin Jeng ◽  
Woei-Cherng Shyu

Evidence has emerged that stem cells represent a promising therapeutic tool for tissue engineering and regenerative medicine. Thus, identifying functional markers for selecting stem cells capable of superior self-renewal and pluripotency (or multipotency) and maintaining stem cell identity under appropriate culture conditions are critical for guiding the use of stem cells toward clinical applications. Many investigations have implicated the insulin-like growth factor 1 receptor (IGF1R) signaling in maintenance of stem cell characteristics and enhancement of stem cell therapy efficacy. IGF1R-expressing stem cells display robust pluripotent or multipotent properties. In this review, we summarize the essential roles of IGF1R signaling in self-renewal, pluripotency (or multipotency), and therapeutic efficacy of stem cells, including human embryonic stem cells, neural stem cells, cardiac stem cells, bone marrow mesenchymal stem cells, placental mesenchymal stem cells, and dental pulp mesenchymal stem cells. Modifying IGF1R signaling may thus provide potential strategies for maintaining stem cell properties and improving stem-cell-based therapeutic applications.


2012 ◽  
Vol 24 (1) ◽  
pp. 215
Author(s):  
B.-R. Yi ◽  
K.-A. Hwang ◽  
K.-C. Choi

When genetically engineered with chemo- or immunotherapeutic genes, stem cells can exhibit a potent therapeutic efficacy combined with their strong tumour tropism. The stem cells were genetically engineered to express a bacterial cytosine deaminase (CD) gene and/or a human interferon-β (IFN-b) gene; thus, 2 stem cell lines, HB1.F3.CD and HB1.F3.CD.IFN-b, were generated, respectively. The CD gene, one of suicide gene, can convert the nontoxic prodrug 5-fluorocytosine (5-FC) to an active form, 5-fluorouracil (5-FU), which has a powerful cytotoxic effect on cancer cells. In addition, human IFN-b is a typical cytokine having an antitumour effect. Using reverse transcription-PCR (RT-PCR), we confirmed CD and/or IFN-b gene expression in HB1.F3 (maternal stem cells) and HB1.F3.CD and HB1.F3.CD.IFN-b cells and the expression of chemoattractant ligands and receptors including stem cell factor (SCF), CXCR4, c-kit, vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) in breast (MCF-7) and endometrial cancer (Ishikawa) cells. To determine the migratory capability of engineered stem cells, we performed a modified trans-well assay. In addition, to identify their therapeutic efficacy, we co-cultured HB1.F3.CD or HB1.F3.CD.IFN-b with breast and endometrial cancer cells and cell viability was measured by MTT assay. The engineered stem cells expressed CD and IFN-b genes and several chemoattractant molecules, SCF, CXCR4, VEGF/VEGFR2 and c-kit, were strongly expressed in breast and endometrial cancer cells. These stem cells were effectively migrated to breast and endometrial cancer cells due to chemoattractant molecules secreted by breast and endometrial cancer cells. In therapeutic efficacy, the viability of breast and endometrial cancer cells treated with 5-FC was reduced in the presence of the HB1.F3.CD and HB1.F3.CD.IFN-b cells. Cell viability was more reduced when co-cultured with HB1.F3.CD.IFN-b compared with HB1.F3.CD cells. In conclusion, the results from the present study suggest that genetically modified stem cells expressing CD and IFN-b can be used as a gene-based therapy for treating breast and endometrial cancer via their tumour tropism. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0005723).


2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Nazmul Haque ◽  
Mohammad Tariqur Rahman ◽  
Noor Hayaty Abu Kasim ◽  
Aied Mohammed Alabsi

Cell-based regenerative therapies, based onin vitropropagation of stem cells, offer tremendous hope to many individuals suffering from degenerative diseases that were previously deemed untreatable. Due to the self-renewal capacity, multilineage potential, and immunosuppressive property, mesenchymal stem cells (MSCs) are considered as an attractive source of stem cells for regenerative therapies. However, poor growth kinetics, early senescence, and genetic instability duringin vitroexpansion and poor engraftment after transplantation are considered to be among the major disadvantages of MSC-based regenerative therapies. A number of complex inter- and intracellular interactive signaling systems control growth, multiplication, and differentiation of MSCs in their niche. Common laboratory conditions for stem cell culture involve ambient O2concentration (20%) in contrast to their niche where they usually reside in 2–9% O2. Notably, O2plays an important role in maintaining stem cell fate in terms of proliferation and differentiation, by regulating hypoxia-inducible factor-1 (HIF-1) mediated expression of different genes. This paper aims to describe and compare the role of normoxia (20% O2) and hypoxia (2–9% O2) on the biology of MSCs. Finally it is concluded that a hypoxic environment can greatly improve growth kinetics, genetic stability, and expression of chemokine receptors duringin vitroexpansion and eventually can increase efficiency of MSC-based regenerative therapies.


2017 ◽  
Author(s):  
Christos Papadimitriou ◽  
Mehmet I. Cosacak ◽  
Violeta Mashkaryan ◽  
Hilal Celikkaya ◽  
Laura Bray ◽  
...  

AbstractThree-dimensional models of human neural development and neurodegeneration are crucial when exploring stem-cell-based regenerative therapies in a tissue-mimetic manner. However, existing 3D culture systems are not sufficient to model the inherent plasticity of NSCs due to their ill-defined composition and lack of controllability of the physical properties. Adapting a glycosaminoglycan-based, cell-responsive hydrogel platform, we stimulated primary and induced human neural stem cells (NSCs) to manifest neurogenic plasticity and form extensive neuronal networks in vitro. The 3D cultures exhibited neurotransmitter responsiveness, electrophysiological activity, and tissue-specific extracellular matrix (ECM) deposition. By whole transcriptome sequencing, we identified that 3D cultures express mature neuronal markers, and reflect the in vivo make-up of mature cortical neurons compared to 2D cultures. Thus, our data suggest that our established 3D hydrogel culture supports the tissue-mimetic maturation of human neurons. We also exemplarily modeled neurodegenerative conditions by treating the cultures with Aβ42 peptide and observed the known human pathological effects of Alzheimer’s disease including reduced NSC proliferation, impaired neuronal network formation, synaptic loss and failure in ECM deposition as well as elevated Tau hyperphosphorylation and formation of neurofibrillary tangles. We determined the changes in transcriptomes of primary and induced NSC-derived neurons after Aβ42, providing a useful resource for further studies. Thus, our hydrogel-based human cortical 3D cell culture is a powerful platform for studying various aspects of neural development and neurodegeneration, as exemplified for Aβ42 toxicity and neurogenic stem cell plasticity.SignificanceNeural stem cells (NSC) are reservoir for new neurons in human brains, yet they fail to form neurons after neurodegeneration. Therefore, understanding the potential use of NSCs for stem cell-based regenerative therapies requires tissue-mimetic humanized experimental systems. We report the adaptation of a 3D bio-instructive hydrogel culture system where human NSCs form neurons that later form networks in a controlled microenvironment. We also modeled neurodegenerative toxicity by using Amyloid-beta4 peptide, a hallmark of Alzheimer’s disease, observed phenotypes reminiscent of human brains, and determined the global gene expression changes during development and degeneration of neurons. Thus, our reductionist humanized culture model will be an important tool to address NSC plasticity, neurogenicity, and network formation in health and disease.


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