STROMAL VASCULAR FRACTION: HARVESTING THE THERAPEUTIC POTENTIAL OF FAT

By Julia Vandewalle 8 months ago
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It was discovered by Zuk et al., in the early 2000’s, that adult fat tissue contains a population of cells very characteristic to that of stem cells [1]. It has since been shown that these cells are easily harvested from fat tissue obtained from a standard liposuction procedure – fat which is commonly discarded as medical waste!

This discovery came after that of bone marrow-derived stem cells in the 1960’s and thus immediately posed as an alternative source of stem cells for use in regenerative therapies. It is not surprising, that since this discovery, adipose stem cells have been the focus of numerous studies and clinical trials.

Creating a great level of confusion with fat-derived stem cells has been the lack of universal consensus on what to call them.  Some of the common names that have been used are: adipose-derived stromal cells (ADSCs), adipose-derived adult stem cells (ASCs), adipose mesenchymal stem cells (AMSCs) and adipose-derived stem cells (ADSCs) [2].

Despite all this, by far the most important thing to be aware of is the distinction between 1) fat-derived cells that are obtained from fat tissue and include a mixture of different cell types and 2) fat-derived cells that are culture expanded within the lab and include fewer cell types [2] [3]. The International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT), stepped in to provide some clarity on the matter and have stated that the former should not be referred to as stem cells but rather stromal vascular fraction (SVF) and the latter to adipose tissue-derived stromal/stem cells (ASCs) (where stromal refers to connective tissue) [4].  ASCs are essentially a type of mesenchymal stem cell [4].

Stromal Vascular Fraction or ‘SVF’ is simply the term used to describe the isolated mixture of cell types found in adult fat. These are the cells that remain after the removal of blood and extracellular fat tissue. To name a few, SVF is comprised of adipose-derived stem/stromal cells, endothelial precursor cells (inner lining of blood vessel), endothelial cells, fibroblasts (cells found in connective tissue), preadipocytes (fat forming cells), macrophages and haematopoietic stem cells (blood forming) [4] [5].

The wonderful thing about SVF is that it may be obtained for autologous use. A patient in need of the regenerative possibilities that SVF has to offer can choose to harvest this cell source from their own fat tissue, allow for it to be processed and then administered to their injured site.  SVF has become of such significant interest in developing cell therapies to date due to the characteristic ability to modulate the immune system and stimulate regeneration [6]. SVF contains a number of different cell types, as well as a type of mesenchymal stem cell, that together have shown to secrete signalling molecules and growth factors that stimulate rejuvenation within the microenvironment of damaged tissue [6].

Clinical application of SVF was first demonstrated in 2008 where it was used to enhance breast augmentations [7]. As of March 2018, 84 clinical trials on ‘stromal vascular fraction’ are presented on www.clinicaltrials.gov.  SVF if being investigated for a vast number of treatments, from pulmonary diseases [8], immune disorders (graft versus host disease and Crohn’s disease) [9] to cartilage regeneration in osteoarthritis [10]  and neuronal diseases (multiple sclerosis) [11].

This rapid rise of the use of SVF and cultured ASCs, due to their immense therapeutic potential in any number of treatments, needs to come with a high level of responsibility. Current controversies linked with fat-derived cell therapies, are due to the lack of an international consensus being reached on the best methods of obtaining and characterising SVF and ASCs [3]. Most countries are still in the process of developing proper regulatory guidelines for stem cell therapies [3]. In this regard, administering facilities need to ensure that patients are always aware of the benefits versus the risks and an informed consent must always be obtained. Patients have an equal responsibility to ensure that they understand the procedure, that they are aware of the risks versus the benefits and that the procedure is being conducted by a well-recognised and accredited facility.

References:

  1. A. Zuk, M. Zhu, H. Mizuno, J. Huang, W. Futrell, A. J. Katz, P. Benhaim, P. Lorenz and M. H. Hedrick, “Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based Therapies,” Tissue Engineering, vol. 7, p. 2, 2001.
  2. Dykstra, T. Facile, R. Patrick, K. Francis, S. Milanovich, J. Weimer and D. Kota, “Concise Review: Fat and Furious: Harnessing the Full Potential of Adipose-Derived Stromal Vascular Fraction,” STEM CELLS Translational Medicine, vol. 6, no. 4, p. 1096–1108, 2017.
  3. Bora and A. Majumdar, “Adipose tissue-derived stromal vascular fraction in regenerative medicine: a brief review on biology and translation.,” Stem Cell Research & Therapy, vol. 8, p. 145, 2017.
  4. Bourin, B. Bunnell, L. Casteilla, M. Dominici, A. Katz, K. March, H. Redl, J. Rubin, K. Yoshimura and J. Gimble, “Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the ISCT,” Cytotherapy, vol. 15, no. 6, pp. 641-8, 2013.
  5. Bora and A. Majumdar, “Adipose tissue-derived stromal vascular fraction in regenerative medicine: a brief review on biology and translation,” Stem Cell Research & Therapy, vol. 8, no. 145, 2017.
  6. Frese , P. Dijkman and S. Hoerstrup, “Adipose Tissue-Derived Stem Cells in Regenerative Medicine,” Transfusion Medicine and Hemotherapy, vol. 43, no. 4, pp. 268-274, 2016.
  7. Yoshimura, K. Sato , N. Aoi , M. Kurita, T. Hirohi and K. Harii, “Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/stromal cells.,” Aesthetic Plast Surgery, vol. 32, no. 1, pp. 48-55, 2008 Jan.
  8. Comella, . J. Blas, T. Ichim, J. Lopez, J. Limon and R. Moreno, “Autologous Stromal Vascular Fraction in the Intravenous Treatment of End-Stage Chronic Obstructive Pulmonary Disease: A Phase I Trial of Safety and Tolerability,” Journal of Clinical Medicine Research, vol. 9, no. 8, p. 701–708, 2017.
  9. Philandrianos, M. Serrero and F. Grimaud, “First Clinical Case Report of Local Microinjection of Autologous Fat and Adipose-Derived Stromal Vascular Fraction for Perianal Fistula in Crohn’s Disease,” Stem Cell Research & Therapy, vol. 9, no. 4, 2018
  10. Pak , J. Lee , K. Park, M. Park, L.-W. Kang and S. Lee, “Current use of autologous adipose tissue-derived stromal vascular fraction cells for orthopedic applications,” Journal of Biomedical Science, vol. 24, no. 9, 2017.
  11. K. Siennicka , A. Zolocinska and K. Stepien K, “Adipose-Derived Cells (Stromal Vascular Fraction) Transplanted for Orthopedical or Neurological Purposes: Are They Safe Enough?,” Stem Cells International, vol. 2016, p. 5762916, 2016.
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 Julia Vandewalle

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