scholarly journals Fundamentals of Stem Cells: Why and How Patients' Own Adult Stem Cells Are the Next Generation of Medicine

Author(s):  
Eckhard U. Alt ◽  
Christoph Schmitz ◽  
Xiaowen Bai

Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold certain promise for regenerative medicine. This paper is intended to clarify and facilitate the understanding, development and adoption of regenerative medicine in general and specifically of therapies based on unmodified, autologous adipose-derived regenerative cells (UA-ADRCs). To this end, results of landmark experiments on stem cells and stem cell therapy performed in the labs of the authors are summarized, the most intriguing of which are the following: (i) vascular associated mesenchymal stem cells (MSCs) can be isolated from different organs (adipose tissue, heart, skin, bone marrow and skeletal muscle) and differentiated into ectoderm, mesoderm and endoderm, providing significant support for the hypothesis of the existence of a small, ubiquitously distributed, universal vascular associated stem cell with full pluripotency; (ii) the orientation and differentiation of MSCs are driven by signals of the respective microenvironment; and (iii) these stem cells irrespective of the tissue origin exhibit full pluripotent differentiation potential without any prior genetic modification or the need for culturing. They can be obtained from a small amount of adipose tissue when using the appropriate technology for isolating the cells, and can be harvested from and re-applied to the same patient at the point of care without the need for complicated processing, manipulation, culturing, expensive equipment, or repeat interventions. These findings demonstrate the potential of UA-ADRCs for triggering the development of an entire new generation of medicine for the benefit of patients and of healthcare systems.

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1097 ◽  
Author(s):  
Eckhard U. Alt ◽  
Glenn Winnier ◽  
Alexander Haenel ◽  
Ralf Rothoerl ◽  
Oender Solakoglu ◽  
...  

It has become practically impossible to survey the literature on cells derived from adipose tissue for regenerative medicine. The aim of this paper is to provide a comprehensive and translational understanding of the potential of UA-ADRCs (uncultured, unmodified, fresh, autologous adipose derived regenerative cells isolated at the point of care) and its application in regenerative medicine. We provide profound basic and clinical evidence demonstrating that tissue regeneration with UA-ADRCs is safe and effective. ADRCs are neither ‘fat stem cells’ nor could they exclusively be isolated from adipose tissue. ADRCs contain the same adult stem cells ubiquitously present in the walls of blood vessels that are able to differentiate into cells of all three germ layers. Of note, the specific isolation procedure used has a significant impact on the number and viability of cells and hence on safety and efficacy of UA-ADRCs. Furthermore, there is no need to specifically isolate and separate stem cells from the initial mixture of progenitor and stem cells found in ADRCs. Most importantly, UA-ADRCs have the physiological capacity to adequately regenerate tissue without need for more than minimally manipulating, stimulating and/or (genetically) reprogramming the cells for a broad range of clinical applications. Tissue regeneration with UA-ADRCs fulfills the criteria of homologous use as defined by the regulatory authorities.


2001 ◽  
Vol 71 (3) ◽  
pp. 178-184
Author(s):  
Ionela Movileanu ◽  
Klara Brinzaniuc ◽  
Marius M. Harpa ◽  
Ovidiu S. Cotoi ◽  
Terezia Preda ◽  
...  

Aim: Our long-term aim is to develop a living valvular substitute using Regenerative Medicine principles, by seeding decellularized porcine heart valve scaffolds with adult stem cells and conditioning them in bioreactors before implantation. In this study, adult stem cells were isolated from sheep adipose tissue (ADSCs). However, we found it impractical to use cells immediately after propagation and thus, in order to extend their availability in time, a preservation method was needed. Methods: Adipose tissue was harvested from 6 sheep. ADSCs were isolated using enzymatic agents and cultured. The cells were tested for plasticity using chondrogenic, adipogenic and osteogenic differentiation kits and then cryopreserved in DMSO at -1400C. Viability was tested after a 3 week storage using Trypan Blue Staining. Results: Ovine ADSCs exhibited excellent plasticity and differentiation potential. An average of 18 million ADSCs were obtained from each ovine, exhibiting more than 88% viability after a 3-week cryopreservation period followed by thawing. Conclusions: DSMO cryopreservation represents a suitable method for ovine ADSCs for regenerative medicine. This method expands the usage of stem cells in vitro before they are differentiated into more specialized cells, offering large numbers of usable ADSCs with minimal cell loss at any desired time point.


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.


2012 ◽  
Vol 1 (1) ◽  
pp. 75-82
Author(s):  
Jordan Greenberg ◽  
Veronica Fortino ◽  
Daniel Pelaez ◽  
Herman S. Cheung

2018 ◽  
Vol 18 (3) ◽  
pp. 264 ◽  
Author(s):  
Roberto Berebichez-Fridman ◽  
Pablo R. Montero-Olvera

First discovered by Friedenstein in 1976, mesenchymal stem cells (MSCs) are adult stem cells found throughout the body that share a fixed set of characteristics. Discovered initially in the bone marrow, this cell source is considered the gold standard for clinical research, although various other sources—including adipose tissue, dental pulp, mobilised peripheral blood and birth-derived tissues—have since been identified. Although similar, MSCs derived from different sources possess distinct characteristics, advantages and disadvantages, including their differentiation potential and proliferation capacity, which influence their applicability. Hence, they may be used for specific clinical applications in the fields of regenerative medicine and tissue engineering. This review article summarises current knowledge regarding the various sources, characteristics and therapeutic applications of MSCs.Keywords: Mesenchymal Stem Cells; Adult Stem Cells; Regenerative Medicine; Cell Differentiation; Tissue Engineering.


Hematology ◽  
2003 ◽  
Vol 2003 (1) ◽  
pp. 398-418 ◽  
Author(s):  
George Q. Daley ◽  
Margaret A. Goodell ◽  
Evan Y. Snyder

Abstract Studies of the regenerating hematopoietic system have led to the definition of many of the fundamental principles of stem cell biology. Therapies based on a range of tissue stem cells have been widely touted as a new treatment modality, presaging an emerging new specialty called regenerative medicine that promises to harness stem cells from embryonic and somatic sources to provide replacement cell therapies for genetic, malignant, and degenerative conditions. Insights borne from stem cell biology also portend development of protein and small molecule therapeutics that act on endogenous stem cells to promote repair and regeneration. Much of the newfound enthusiasm for regenerative medicine stems from the hope that advances in the laboratory will be followed soon thereafter by breakthrough treatments in the clinic. But how does one sort through the hype to judge the true promise? Are stem cell biologists and the media building expectations that cannot be met? Which diseases can be treated, and when can we expect success? In this review, we outline the realms of investigation that are capturing the most attention, and consider the current state of scientific understanding and controversy regarding the properties of embryonic and somatic (adult) stem cells. Our objective is to provide a framework for appreciating the promise while at the same time understanding the challenges behind translating fundamental stem cell biology into novel clinical therapies.


2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Saman Ghoraishizadeh ◽  
Afsoon Ghorishizadeh ◽  
Peyman Ghoraishizadeh ◽  
Nasibeh Daneshvar ◽  
Mohadese Hashem Boroojerdi

Regenerative medicine is an alternative solution for organ transplantation. Stem cells and nanoscaffolds are two essential components in regenerative medicine. Mesenchymal stem cells (MSCs) are considered as primary adult stem cells with high proliferation capacity, wide differentiation potential, and immunosuppression properties which make them unique for regenerative medicine and cell therapy. Scaffolds are engineered nanofibers that provide suitable microenvironment for cell signalling which has a great influence on cell proliferation, differentiation, and biology. Recently, application of scaffolds and MSCs is being utilized in obtaining more homogenous population of MSCs with higher cell proliferation rate and greater differentiation potential, which are crucial factors in regenerative medicine. In this review, the definition, biology, source, characterization, and isolation of MSCs and current report of application of nanofibers in regenerative medicine in different lesions are discussed.


2020 ◽  
Vol 21 (2) ◽  
pp. 1-8
Author(s):  
Afadhali Denis Russa

Stem cell technology and its application in regenerative medicine is the future gateway for the treatment of most non-communicable diseases (NCDs). As the burden of NCDs continues to rises globally, regenerating the cells, tissues and organs will be the mainstream treatment option. The world is prepared for this intriguing but promising avenue of biomedical technology and medicine but Africa is grossly lagging far behind. African governments, universities, research and health institutions need to take a leading role in empowering and mainstreaming stem cell research.  Moreover, for Africa, there is a huge potential for translating stem cell technology into clinical treatments due to the fact that there are limited treatment options for life-threatening forms of NCDs.  Some African countries have well-developed stem cell facilities and large-scale stem cell therapy centers. The use of adult stem cells in liver failure, diabetes and cardiac infarcts has shown success in some African countries. The present work reviews the status, potential and future prospects of stem cell technology and regenerative medicine in Tanzania with particular emphasis on the adult stem cells applicability into the immediate use inpatient care.  The paper also reviews the available cell identification systems and markers and moral and ethical aspects of stem cell science necessary in the translational treatment regimens. 


2020 ◽  
Author(s):  
Benjamin A Yang ◽  
Jesus A Castor-Macias ◽  
Paula M Fraczek ◽  
Lemuel A Brown ◽  
Myungjin Kim ◽  
...  

The health and homeostasis of skeletal muscle is preserved by a population of tissue resident stem cells called satellite cells. Young healthy satellite cells maintain a state of quiescence, but aging or metabolic insults results in reduced capacity to prevent premature activation and stem cell exhaustion. As such, understanding genes and pathways that protect satellite cell maintenance of quiescence are needed. Sestrins are a class of stress-inducible proteins that act as antioxidants and inhibit the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling complex. Despite these pivotal roles, the role of Sestrins has not been explored in adult stem cells. Herein, we show that Sestrin1,2 loss results in hyperactivation of the mTORC1 complex, increased propensity to enter the cell cycle and shifts in metabolic flux. Aging of Sestrin1,2 knockout mice demonstrated a loss of MuSCs and reduced ability to regenerate. These findings demonstrate Sestrins function to help maintain MuSC metabolism that supports quiescence and against aging.


2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Mario F. Muñoz ◽  
Sandro Argüelles ◽  
Francesco Marotta ◽  
Mario Barbagallo ◽  
Mercedes Cano ◽  
...  

A wide range of clinical applications in regenerative medicine were opened decades ago with the discovery of adult stem cells. Highly promising adult stem cells are mesenchymal stem/stromal cells derived from adipose tissue (ADSCs), primarily because of their abundance and accessibility. These cells have multipotent properties and have been used extensively to carry out autologous transplants. However, the biology of these cells is not entirely understood. Among other factors, the regeneration capacity of these cells will depend on both their capacity of proliferation/differentiation and the robustness of the biochemical pathways that allow them to survive under adverse conditions like those found in damaged tissues. The transcription factors, such as Nanog and Sox2, have been described as playing an important role in stem cell proliferation and differentiation. Also, the so-called longevity pathways, in which AMPK and SIRT1 proteins play a crucial role, are essential for cell homeostasis under stressful situations. These pathways act by inhibiting the translation through downregulation of elongation factor-2 (eEF2). In order to deepen knowledge of mesenchymal stem cell biology and which factors are determinant in the final therapeutic output, we evaluate in the present study the levels of all of these proteins in the ADSCs from humans and rats and how these levels are affected by aging and the oxidative environment. Due to the effect of aging and oxidative stress, our results suggest that before performing a cell therapy with ADSCs, several aspects reported in this study such as oxidative stress status and proliferation and differentiation capacity should be assessed on these cells. This would allow us to know the robustness of the transplanted cells and to predict the therapeutic result, especially in elder patients, where probably ADSCs do not carry out their biological functions in an optimal way.


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