Therapeutic potential of transdifferentiated cells

2005 ◽  
Vol 108 (4) ◽  
pp. 309-321 ◽  
Author(s):  
Zoë D. BURKE ◽  
David TOSH

Cell therapy means treating diseases with the body's own cells. The ability to produce differentiated cell types at will offers a compelling new approach to cell therapy and therefore for the treatment and cure of a plethora of clinical conditions, including diabetes, Parkinson's disease and cardiovascular disease. Until recently, it was thought that differentiated cells could only be produced from embryonic or adult stem cells. Although the results from stem cell studies have been encouraging, perhaps the most startling findings have been the recent observations that differentiated cell types can transdifferentiate (or convert) into a completely different phenotype. Harnessing transdifferentiated cells as a therapeutic modality will complement the use of embryonic and adult stem cells in the treatment of degenerative disorders. In this review, we will examine some examples of transdifferentiation, describe the theoretical and practical issues involved in transdifferentiation research and comment on the long-term therapeutic possibilities.

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Maximiliano I. Schaun ◽  
Bruna Eibel ◽  
Melissa Kristocheck ◽  
Grasiele Sausen ◽  
Luana Machado ◽  
...  

The incidence of severe ischemic heart disease caused by coronary obstruction has progressively increased. Alternative forms of treatment have been studied in an attempt to regenerate myocardial tissue, induce angiogenesis, and improve clinical conditions. In this context, cell therapy has emerged as a promising alternative using cells with regenerative potential, focusing on the release of paracrine and autocrine factors that contribute to cell survival, angiogenesis, and tissue remodeling. Evidence of the safety, feasibility, and potential effectiveness of cell therapy has emerged from several clinical trials using different lineages of adult stem cells. The clinical benefit, however, is not yet well established. In this review, we discuss the therapeutic potential of cell therapy in terms of regenerative and angiogenic capacity after myocardial ischemia. In addition, we addressed nonpharmacological interventions that may influence this therapeutic practice, such as diet and physical training. This review brings together current data on pharmacological and nonpharmacological approaches to improve cell homing and cardiac repair.


2008 ◽  
Vol 24 (3-4) ◽  
pp. E18 ◽  
Author(s):  
Matthew T. Harting ◽  
James E. Baumgartner ◽  
Laura L. Worth ◽  
Linda Ewing-Cobbs ◽  
Adrian P. Gee ◽  
...  

Preliminary discoveries of the efficacy of cell therapy are currently being translated to clinical trials. Whereas a significant amount of work has been focused on cell therapy applications for a wide array of diseases, including cardiac disease, bone disease, hepatic disease, and cancer, there continues to be extraordinary anticipation that stem cells will advance the current therapeutic regimen for acute neurological disease. Traumatic brain injury is a devastating event for which current therapies are limited. In this report the authors discuss the current status of using adult stem cells to treat traumatic brain injury, including the basic cell types and potential mechanisms of action, preclinical data, and the initiation of clinical trials.


2019 ◽  
pp. S131-S138 ◽  
Author(s):  
A. SAMAKOVA ◽  
A. GAZOVA ◽  
N. SABOVA ◽  
S. VALASKOVA ◽  
M. JURIKOVA ◽  
...  

Ischemic diseases are characterized by reduced blood supply to a tissue or an organ due to obstruction of blood vessels. The most serious and most common ischemic diseases include ischemic heart disease, ischemic stroke, and critical limb ischemia. Revascularization is the first choice of therapy, but the cell therapy is being introduced as a possible way of treatment for no-option patients. One of the possibilities of cell therapy is the use of mesenchymal stem cells (MSCs). MSCs are easily isolated from bone marrow and can be defined as non-hematopoietic multipotent adult stem cells population with a defined capacity for self-renewal and differentiation into cell types of all three germ layers depending on their origin. Since 1974, when Friedenstein and coworkers (Friedenstein et al. 1974) first time isolated and characterized MSCs, MSC-based therapy has been shown to be safe and effective. Nevertheless, many scientists and clinical researchers want to improve the success of MSCs in regenerative therapy. The secret of successful cell therapy may lie, along with the homing, in secretion of biologically active molecules including cytokines, growth factors, and chemokines known as MSCs secretome. One of the intracellular signalling mechanism includes the activity of phosphatidylinositol-3-kinase (phosphoinositide 3-kinase) (PI3K) - protein kinase B (serine-threonine protein kinase Akt) (Akt) pathway. This PI3K/Akt pathway plays key roles in many cell types in regulating cell proliferation, differentiation, apoptosis, and migration. Pre-conditioning of MSCs could improve efficacy of signalling mechanism.


2021 ◽  
Vol 22 (2) ◽  
pp. 970
Author(s):  
Quan-Wen Liu ◽  
Qi-Ming Huang ◽  
Han-You Wu ◽  
Guo-Si-Lang Zuo ◽  
Hao-Cheng Gu ◽  
...  

Stem cells including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells (ASCs) are able to repair/replace damaged or degenerative tissues and improve functional recovery in experimental model and clinical trials. However, there are still many limitations and unresolved problems regarding stem cell therapy in terms of ethical barriers, immune rejection, tumorigenicity, and cell sources. By reviewing recent literatures and our related works, human amnion-derived stem cells (hADSCs) including human amniotic mesenchymal stem cells (hAMSCs) and human amniotic epithelial stem cells (hAESCs) have shown considerable advantages over other stem cells. In this review, we first described the biological characteristics and advantages of hADSCs, especially for their high pluripotency and immunomodulatory effects. Then, we summarized the therapeutic applications and recent progresses of hADSCs in treating various diseases for preclinical research and clinical trials. In addition, the possible mechanisms and the challenges of hADSCs applications have been also discussed. Finally, we highlighted the properties of hADSCs as a promising source of stem cells for cell therapy and regenerative medicine and pointed out the perspectives for the directions of hADSCs applications clinically.


2021 ◽  
pp. 1-18
Author(s):  
Jonathan Slack

‘What are stem cells?’ explains that a stem cell is a cell that can both reproduce itself and generate offspring of different functional cell types and begins by considering the nature of cells in general, wherein cells are understood to be the ultimate structural unit of an animal or plant body. Stem cells in the body persist long term, usually for the lifetime of the organism. Good examples of differentiated cells arising from stem cells are those of the skin, the blood, and the lining of the intestine. Embryonic stem cells are grown in culture from early mammalian embryos. The reason that stem cell research is seen as the source for new cures is largely because this technology offers a route to cell therapy.


Author(s):  
Silvia Barbon ◽  
Senthilkumar Rajendran ◽  
Thomas Bertalot ◽  
Monica Piccione ◽  
Marco Gasparella ◽  
...  

Abstract Background: Stem cell therapy is gaining momentum as an effective treatment strategy for degenerative diseases. Adult stem cells isolated from various sources (i.e., cord blood, bone marrow, adipose tissue) are being considered as a realistic option due to their well-documented therapeutic potentials. Our previous studies standardized a method to isolate circulating multipotent cells (CMCs) that are able to sustain long term in vitro culture and differentiate towards mesodermal lineages. Methods: In this work, long-term cultures of CMCs were stimulated to study in vitro neuronal and myogenic differentiation. After induction, cells were analysed at different time points. Morphological studies were performed by scanning electron microscopy and specific neuronal and myogenic marker expression were evaluated using RT-PCR, flow cytometry and western blot. For myogenic plasticity study, CMCs were transplanted into in vivo model of chemically-induced muscle damage. Results: After neurogenic induction, CMCs showed characteristic dendrite-like morphology and expressed specific neuronal markers both at mRNA and protein level. The calcium flux activity of CMCs under stimulation with potassium chloride and the secretion of noradrenalin confirmed their ability to acquire a functional phenotype. In parallel, the myogenic potential of CMCs was confirmed by their ability to form syncytium-like structures in vitro and express myogenic markers both at early and late phases of differentiation. Interestingly, in a rat model of bupivacaine-induced muscle damage, CMCs integrated within the host tissue taking part in tissue repair. Conclusion: Overall, collected data demonstrated long-term cultured CMCs retain proliferative and differentiative potentials suggesting to be a good candidate for cell therapy.


2021 ◽  
Author(s):  
Gabriela Guy Duarte ◽  
Daniel Gonçalves de Oliveira ◽  
Felipe de Oliveira Breder ◽  
Guilherme Augusto Netto Nacif ◽  
Ivan Magalhães Viana

Background: Ischemic stroke is one of the main causes of long-term disability in adults. In the search for therapies for neurological sequelae after stroke, several studies have been investigating the use of stem cells, especially mesenchymal stem cells (MSC). Objectives: To evaluate the efficacy of stem cell therapy in patients with neurological deficits due to stroke. Methods: A literature review was conducted based on clinical studies published on PubMed and Cochrane databases between 2013 and 2021. The search strategy (mesenchymal stem cells) AND (stroke) was used and 4 articles were selected. Results: In the selected studies, we observed the use of autologous or allogeneic MSCs, derived from bone marrow or umbilical cord. The cells were transplanted using intravenous, intra-arterial or intracerebral routes. The articles demonstrated safety in the use of MSC, with no reports of serious adverse effects causally related to cell therapy. The evaluation of efficacy was performed through the analysis of neurological condition scales such as the NIHSS, the modified Rankin Scale and the Fugl-Meyer Scale. The trials showed improvements in at least one of the scales after therapy, and the benefits focused, mainly, on the motor function of the patients. MSC are associated with the secretion of factors that promote inflammatory immunomodulation, angiogenesis and neurogenesis, contributing to brain repair. Conclusions: The use of MSCs in the treatment of ischemic stroke is safe and has therapeutic potential for repairing ischemic brain tissue. However, further studies are needed to prove the efficacy of MSCs in the rehabilitation of stroke.


Nano LIFE ◽  
2019 ◽  
Vol 09 (03) ◽  
pp. 1941002
Author(s):  
Yanbin Fu ◽  
Zhiying He ◽  
Chao Zhang

Stem cell therapy is being developed as a promising novel strategy for the treatment of heart-associated diseases. Several types of cells such as skeletal myoblasts, bone marrow (BM) mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), adipose stem cells (ADSCs), cardiac progenitor cells (CPCs), induced pluripotent stem cells (iPSCs) have been tested in pre-clinical and clinical cardiac repairing models. Fibroblasts, as terminally differentiated cells, could also be trans-differentiated into cardiomyocytes in vitro. In this review, we will summarize the recent advances of cell types, potential applications and challenges of stem cell therapy in the treatment of heart failure.


Author(s):  
Gary Hin-Fai Yam ◽  
Gary Swee-Lim Peh ◽  
Shweta Singhal ◽  
Bee-Tin Goh ◽  
Jodhbir S. Mehta

Regenerative medicine using patient's own stem cells (SCs) to repair dysfunctional tissues is an attractive approach to complement surgical and pharmacological treatments for aging and degenerative disorders. Recently, dental SCs have drawn much attention owing to their accessibility, plasticity and applicability for regenerative use not only for dental, but also other body tissues. In ophthalmology, there has been increasing interest to differentiate dental pulp SC and periodontal ligament SC (PDLSC) towards ocular lineage. Both can commit to retinal fate expressing eye field transcription factors and generate rhodopsin-positive photoreceptor-like cells. This proposes a novel therapeutic alternative for retinal degeneration diseases. Moreover, as PDLSC shares similar cranial neural crest origin and proteoglycan secretion with corneal stromal keratoctyes and corneal endothelial cells, this offers the possibility of differentiating PDLSC to these corneal cell types. The advance could lead to a shift in the medical management of corneal opacities and endothelial disorders from highly invasive corneal transplantation using limited donor tissue to cell therapy utilizing autologous cells. This article provides an overview of dental SC research and the perspective of utilizing dental SCs for ocular regenerative medicine.


2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Dilip Dey ◽  
Gregory R. D. Evans

During embryonic development pluripotency is progressively lost irreversibly by cell division, differentiation, migration and organ formation. Terminally differentiated cells do not generate other kinds of cells. Pluripotent stem cells are a great source of varying cell types that are used for tissue regeneration or repair of damaged tissue. The pluripotent stem cells can be derived from inner cell mass of blastocyte but its application is limited due to ethical concerns. The recent discovery of iPS with defined reprogramming factors has initiated a flurry of works on stem cell in various laboratories. The pluripotent cells can be derived from various differentiated adult cells as well as from adult stem cells by nuclear reprogramming, somatic cell nuclear transfer etc. In this review article, different aspects of nuclear reprogramming are discussed.


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