scholarly journals Towards a Comprehensive Understanding of UA-ADRCs (Uncultured, Autologous, Fresh, Unmodified, Adipose Derived Regenerative Cells, Isolated at Point of Care) in Regenerative Medicine

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.

Author(s):  
Eckhard Alt ◽  
Glenn Winnier ◽  
Alexander Haenel ◽  
Ralf Rothoerl ◽  
Oender Solakoglu ◽  
...  

It has become practically impossible to survey the literature on cells derived from adipose tissue with the aim to apply them in regenerative medicine. The aim of this review is to provide a jump start to understanding the potential of UA-ADRCs (uncultured, unmodified, fresh, autologous adipose derived regenerative cells isolated at the point of care) in regenerative medicine. We show that serious and adequate clinical research demonstrates 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, as ADRCs contain the same adult (depending on the definition) pluripotent or multipotent stem cells that are ubiquitously present in the walls of small blood vessels. Of note, the specific isolation procedure used has significant impact on the number and viability of the cells and hence on safety and efficacy of UA-ADRCs. Furthermore, there is no need to further separate adipose-derived stem cells (ASCs) from ADRCs if the latter were adequately isolated from adipose tissue. Most importantly, UA-ADRCs have the physiological capacity to adequately regenerate tissue without need for manipulating, stimulating and/or (genetically) reprogramming the cells for this purpose. Tissue regeneration with UA-ADRCs fulfills the criteria of homologous use.


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.


2021 ◽  
Vol 22 (2) ◽  
pp. 763
Author(s):  
Vitale Miceli ◽  
Matteo Bulati ◽  
Gioacchin Iannolo ◽  
Giovanni Zito ◽  
Alessia Gallo ◽  
...  

Mesenchymal stromal/stem cells (MSCs) are multipotent adult stem cells that support homeostasis during tissue regeneration. In the last decade, cell therapies based on the use of MSCs have emerged as a promising strategy in the field of regenerative medicine. Although these cells possess robust therapeutic properties that can be applied in the treatment of different diseases, variables in preclinical and clinical trials lead to inconsistent outcomes. MSC therapeutic effects result from the secretion of bioactive molecules affected by either local microenvironment or MSC culture conditions. Hence, MSC paracrine action is currently being explored in several clinical settings either using a conditioned medium (CM) or MSC-derived exosomes (EXOs), where these products modulate tissue responses in different types of injuries. In this scenario, MSC paracrine mechanisms provide a promising framework for enhancing MSC therapeutic benefits, where the composition of secretome can be modulated by priming of the MSCs. In this review, we examine the literature on the priming of MSCs as a tool to enhance their therapeutic properties applicable to the main processes involved in tissue regeneration, including the reduction of fibrosis, the immunomodulation, the stimulation of angiogenesis, and the stimulation of resident progenitor cells, thereby providing new insights for the therapeutic use of MSCs-derived products.


2012 ◽  
Vol 4 (2) ◽  
pp. 59
Author(s):  
Yani Lina ◽  
Andi Wijaya

BACKGROUND: The potential use of stem cell-based therapies for repair and regeneration of various tissues and organs offers a paradigm shift that may provide alternative therapeutic solutions for a number of disease. Despite the advances, the availability of stem cells remaining a challenge for both scientist and clinicians in pursuing regenerative medicine. CONTENT: Subcutaneous human adipose tissue is an abundant and accessible cell source for applications in tissue engineering and regenerative medicine. Routinely, the adipose issue is digested with collagenase or related lytic enzymes to release a heterogeneous population for stromal vascular fraction (SVF) cells. The SVF cells can be used directly or can be cultured in plastic ware for selection and expansion of an adherent population known as adipose-derived stromal/stem cells (ASCs). Their potential in the ability to differentiate into adipogenic, osteogenic, chondrogenic and other mesenchymal lineages, as well in their other clinically useful properties, includes stimulation of angiogenesis and suppression of inflammation.SUMMARY: Adipose tissue is now recognized as an accessible, abundant and reliable site for the isolation of adult stem cels suitable for the application of tissue engineering and regenerative medicine applications. The past decade has witnessed an explosion of preclinical data relating to the isolation, characterization, cryopreservation, differentiation, and transplantation of freshly isolated stromal vascular fraction cells and adherent, culture-expanded, adipose-derived stromal/stem cells in vitro and in animal models.KEYWORDS: adipose tissue, adult stem cells, regenerative medicine, mesenchymal stem cells


2020 ◽  
Vol 15 (3) ◽  
pp. 284-299
Author(s):  
Nur S. Aziz ◽  
Norhayati Yusop ◽  
Azlina Ahmad

Stem cells play an essential role in maintaining homeostasis, as well as participating in new tissue regeneration. Over the past 20 years, a great deal of effort has been made to investigate the behaviour of stem cells to enable their potential use in regenerative medicine. However, a variety of biological characteristics are known to exist among the different types of stem cells due to variations in the methodological approach, formulation of cell culture medium, isolation protocol and cellular niches, as well as species variation. In recent years, cell-based therapy has emerged as one of the advanced techniques applied in both medical and clinical settings. Cell therapies aim to treat and repair the injury sites and replace the loss of tissues by stimulating the repair and regeneration process. In order to enable the use of stem cells in regenerative therapies, further characterisation of cell behaviour, in terms of their proliferation and differentiation capacity, mainly during the quiescent and inductive state is regarded as highly necessary. The central focus of regenerative medicine revolves around the use of human cells, including adult stem cells and induced pluripotent stem cells for cell-based therapy. The purpose of this review was to examine the existing body of literature on stem cell research conducted on cellular angiogenesis and migration, to investigate the validity of different strategies and variations of the cell type used. The information gathered within this review may then be shared with fellow researchers to assist in future research work, engaging in stem cell homing for cell-based therapy to enhance wound healing and tissue regeneration process.


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.


2013 ◽  
Vol 10 (1) ◽  
pp. 8-18 ◽  
Author(s):  
Soyoung Shin ◽  
Yonggoo Kim ◽  
Sikyoung Jeong ◽  
Sungyoup Hong ◽  
Insoo Kim ◽  
...  

Author(s):  
Laura Aust ◽  
Lyndon Cooper ◽  
Blythe Devlin ◽  
Tracey du Laney ◽  
Sandra Foster ◽  
...  

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

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