A quick addition just for @crazyivan. Here’s an excerpt form a bibliographical review, complete with bibliography at the end should you care to delve into the topic a bit more. I remind you, this is only an excerpt… but you can find more than enough reading material from the bibliography provided at the end.
Enjoy.
Adult Stem Cells (ASCs), by definition, are unspecialized or undifferentiated cells that not only retain their ability to divide mitotically while still maintaining their undifferentiated state but also given the right conditions, have the ability to differentiate into different types of cells including cells of different germ-origin – an ability referred to as transdifferentiation or plasticity.1,2 In vitro, the conditions under which transdifferentiation occurs can be brought about by modifying the culture medium in which the cells are cultured. In vivo, the same changes are seen when the ASCs are transplanted into a tissue environment different to their own tissue-of origin. Though the exact mechanism of this transdifferentiation of ASCs is still under debate, this ability of ASCs along with their ability to self-renew is of great interest in the field of Regenerative Medicine as a therapeutic tool in being able to regenerate and replace dying, damaged or diseased tissue.
Clinically, however, there are a few criteria that ASCs need to fulfill before they can be viewed as a viable option in Regenerative Medicine. These are as follows:3
1. Abundance in numbers (millions to billions of cells)
2. Ease of harvest (through minimally invasive procedures)
3. Ability to differentiate into multiple cell types (which can be regulated and reproduced in vitro)
4. Safe to transplant to a different site of the autologous host or even an allogenic host.
5. No conflict with current Good Manufacturing Principles (during procurement, culture or transplantation)
Adipose Tissue Yields an Abundance of ASC’s
Compared to any other source, the vast amounts of adipose tissue (depots of fat for storing energy) especially in the abdominal region, by sheer volume of availability, ensure an abundance in numbers of ASCs ranging in the millions per unit volume. The sheer numbers available also has the added advantage of not needing to be cultured in a laboratory over days in order to get the desired number of ASCs to achieve what is called “therapeutic threshold” i.e. therapeutic benefit. In addition, harvesting ASCs from adipose tissue through simple, minimally invasive liposuction under local anesthesia is relatively easier, painless and poses minimal risk to the patient compared to all other possible methods.
Adipose tissue ASCs (AT-ASCs) are extremely similar to stem cells isolated from bone marrow (BMSCs). The similarities in profile between the two types of ASCs range from morphology to growth to transcriptional and cell surface phenotypes.4,5 Their similarity extends also to their developmental behavior both in vitro and in vivo. This has led to suggestions that adipose-derived stem cells are in fact a mesenchymal stem cell fraction present within adipose tissue.6
Clinically, however, stromal vascular fraction-derived AT-ASCs have the advantage over their bone marrow-derived counterparts, because of their abundance in numbers – eliminating the need for culturing over days to obtain a therapeutically viable number – and the ease of the harvest procedure itself – being less painful than the harvest of bone marrow. This, in theory, means that an autologous transplant of adipose-derived ASCs will not only work in much the same way as the successes shown using marrow-derived mesenchymal stem cell transplant, but also be of minimal risk to the patient.
AT-ASCs, like BM-ASCs, are called Mesenchymal ASCs because they are both of mesodermal germ-origin. This means that AT-ASCs are able to differentiate into specialized cells of mesodermal origin such as adipocytes, fibroblasts, myocytes, osteocytes and chondrocytes.7,8,9 AT-ASCs are also able to, given the right conditions of growth factors, transdifferentiate into cells of germ-origin other than their own. Animal model and human studies have shown AT-ASCs to undergo cardiomyogenic 10, endothelial (vascular)11, pancreatic (endocrine) 12, neurogenic 13, and hepatic trans-differentiation14 , while also supporting haematopoesis15.
Low Risk to the Patient
Autologous transplant of SVF AT-ASCs also poses extremely low risk to the patient when done as a single procedure in a sterile surgical operating room setting. Furthermore, it is postulated that SVF AT-ASCs due to their immunosuppressive properties may be transplanted into not only autologous but also allogenic tissues without initiating a cytotoxic T-cell response.16 We at AdiStem believe autologous transplant to be the safest and most viable option at this point.
It is noteworthy that the protocol devised by AdiStem for the procurement of SVF AT-ASCs does not overlook the therapeutic potential conferred by the cocktail of ingredients present in the SVF. Let us look at this cocktail of cells, proteins and growth factors in a little more detail.
The extracellular matrix of adipose tissue contains different types of Collagen such as Types 1, 3–4, 7, 14–15, 18 and 27 to name a few.6 This is important in AdiStem’s Fat Transfer protocol where freshly isolated fat is used as a filler in augmentation or post-lumpectomy reconstruction of the breast and in the augmentation of the penis, and where collagen provides the structural support required for cell survival.
Furthermore, the extracellular matrix plays an important role in adipocyte endocrine secretions, and release of growth factors such as transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF), among others all of which are contained in the SVF.17 This is consistent with the secretions of cells in the presence of an extracellular matrix. The SVF also contains the various proteins present in the adipose tissue extracellular matrix of which Laminin is of interest due to its ability to help in neural regeneration.6
The cellular composition of the SVF ranges from pre-adipocytes to endothelial cells, smooth muscle cells, pericytes, fibroblasts, and AT-ASCs. Typically, the SVF also contains blood cells from the capillaries supplying the fat cells. These include erythrocytes, B and T cells, macrophages, monocytes, mast cells, natural killer (NK) cells, hematopoietic stem cells and endothelial progenitor cells, to name a few. The latter two types of cells, namely the hematopoietic stem cells and endothelial progenitor cells play important roles in supporting the viability of existing blood vessels and helping create new ones respectively.
We believe that these other ingredients that make up the SVF ‘cocktail’ act as an adjuvant to further augment the effect of the autologous transplant of SVF AT-ASCs.
References
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2 Filip S, Mokrý J, Hruška I (2003) Adult stem cells and their importance in cell therapy. Folia Biol.(Prague) 49: 9–14.
3 Gimble JM, Katz AJ, Bunnell BA (2007) Adipose-derived Stem Cells for Regenerative Medicine Circ Res. 100:1249–1260.
4 Katz AJ, Tholpady A, Tholpady SS, et al. (2005) Cell surface and transcriptional characterization of human adipose-derived adherent stromal (hADAS) cells. Stem Cells 23(3):412–23.
5 Pittenger MF, Martin BJ. (2004) Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res. 95(1):9–20.
6 Tholpady SS, Llull R, Ogle RC, et al. ((2006) Adipose Tissue: Stem Cells and Beyond. Clin Plastic Surg 33:55–62
7 Zuk PA, Zhu M, Mizuno H, Huang JI, Chaudhari S, Lorenz HP, Benhaim P and Hedrick MH (2001). “Mutilineage cells derived from human adipose tissue: a putative source of stem cells for tissue engineering”. Tissue Engineering 7 (2): 211–216.
8 Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P and Hedrick MH (2002). “Human adipose tissue is a source of multipotent stem cells”. Mol Biol Cell 13: 4279–4295.
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