By virtue of their function, there are two distinct types of Stem Cells. One that is responsible for the development of an embryo from a single cell, by giving rise to specialized embryonic tissues, and resulting ultimately in the development of a human fetus; and the other which acts as the body’s repair mechanism by differentiating into specialized cells to replace damaged cells with healthy ones. These two types of stem cells are called Embryonic Stem Cells and Adult Stem Cells respectively. 1
Stem cells are different from other cells in the human body in two ways. First is that they are unspecialized or undifferentiated cells that have the ability to self-renew through mitotic cell division while still maintaining their undifferentiated state. This is called Symmetric cell division where both daughter cells retain the parent stem cell properties. 2
Second, is their ability to differentiate into different types of specialized cells while still maintaining their original numbers. Stem cells are able to do this through a process called Asymmetric Cell Division, where one of the two daughter cells differentiates into what is known as a progenitor cell, while the other daughter cell remains undifferentiated, thus retaining its parent stem cell properties. 2
Compared to a stem cell, a progenitor cell only has a limited ability for self-renewal; and following a limited number of rounds of cell division, the resulting progenitor cells differentiate into specialized cells of the body. 3
ASCs are generally ‘multipotent’ lineage-restricted cells with the ability to only differentiate into types of cells predetermined by the germ layer-origin of the tissue within which they reside. However, in vitro studies have shown that, given the right conditions, some ASCs can differentiate into cell types of germ-origin different to their tissue of origin. This is called Trans-differentiation or Plasticity. 4 , 5 , This makes these ASCs ‘pluripotent’ and hence very attractive in on-going stem cell research to find ways of culturing and transplanting healthy cells to replace diseased, damaged or dying tissues. 6
ASCs can be described in a number of ways depending on their potency, germ layer of origin, or their tissue of origin. For example, ASCs present in adipose tissue may be called Multipotent, Mesenchymal, Adipose-derived, ASCs. However, a more accurate description of ASCs harvested, isolated and activated using the AdiStem protocol would be to refer to them as Stromal Vascular Fraction-derived Adipose Tissue Mesenchymal Stem Cells (SVF-derived AT-MSCs)
ASCs are sometimes also referred to as Somatic (from Greek S?µat??ó?, of the body) stem cells.
These include erythrocytes or red blood cells, B and T cells, macrophages, monocytes, mast cells, natural killer (NK) cells, hematopoietic stem cells and endothelial progenitor cells, to name a few. Furthermore, SVF, in addition to the adipocyte endocrine secretions, also contains growth factors such as transforming growth factor beta (TGF-?), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF), among others. 7
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. 8
The sheer number of ASCs that can be harvested at any one time from fat makes this the best source of ASCs in the human body. This number of ASCs harvested from fat 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 is relatively easier, painless and poses minimal risk to the patient.
AdiStem Pty. Ltd. has researched the effect of different monochromatic light intensities and frequencies in the colored spectrum on various human and animal cell populations such as mesenchyme stem cells and white blood cells.
Low-level light photoactivation or photomodulation can be utilized for significant benefit in the stimulation of proliferation, differentiation, and inhibition/induction release of growth factors/cytokines of cells from any living organism.
The wavelength or bandwidth of wavelengths is one of the critical factors in selective photomodulation. Pulsed or continuous exposure, duration and frequency of pulses (and dark ‘off’ period) and energy are also factors as well as the presence, absence or deficiency of any or all cofactors, enzymes, catalysts, or other building blocks of the process being photomodulated.
Different parameters with the same wavelength may have very diverse and even opposite effects. When different parameters of photomodulation are performed simultaneously, different effects may be produced. When different parameters are used serially or sequentially, the effects are also different. The selection of wavelength photomodulation is critical as is the bandwidth selected as there may be a very narrow bandwidth for some applications — in essence these are biologically active spectral intervals.
AdiStem has ongoing international research projects looking at the effects of different frequencies of monochromatic lights on various cells including mesenchyme stem cells and white blood cells. It has now found five frequencies (three are present in AdiLight-2) that can activate stem cells, in vitro, and two frequencies that inhibit them. AdiStem has also found similar frequencies to modulate pro-inflammatory and anti-inflammatory cytokine release from peripheral blood white blood cells. AdiStem is also exploring the direct effect of different low-level frequencies of light on endogenous cells (in vivo).
AdiLight-2 is available from AdiStem for use in activating mesenchyme stem cells and modulating cytokine release by white blood cells.
Mesenchyme Stem Cells
When adipose-derived mesenchyme stem cells are taken out of a subject most of the cells are in a dormant state. In the body, stem cells and progenitor cells need to be activated by a physiological repair mechanism cascade, for example release of growth factor and chemokines by platelets. When the adipose-derived stem cells are photoactivated for 20 minutes with the AdiLight-2 device they show increased proliferation, increased production of integrins, vascular endothelial growth factor, thymosin beta 4 and interleukin 1 receptor antagonist. Hence, AdiLight-2 is of value in providing consistent clinical results, especially amongst age differences.
Peripheral Blood White Blood Cells
For many years internal medicine specialists in Eastern Europe and Korea have been using the photoactivation of blood, in vitro and in vivo, with various frequencies of light for immunomodulation in patients. When peripheral blood white blood cells (WBC) are photoactivated under AdiLight-2 for 10 minutes, an inhibition of pro-inflammatory cytokines (IL1, IL2, IL6 and TNFalpha) and induction of anti-inflammatory cytokines (IL1Ra and IL10) and beta endorphins are observed.
Reduces Pain and Accelerates Healing
Because of this property we have found AdiLight-2 to be a beneficial add-on to commonly used platelet rich plasma procedures in orthopedic and sports medicine procedures. One of the largest clinical drawbacks of the use of PRP in musculoskeletal healing is the aggravation of pain observed in the injected area post injection. Working with a group of Australian sports medicine specialists, we have deduced that a 10-minute exposure of WBC and platelets to AdiLight-2 prior to injection eliminates the aggravation of pain and potentiates the accelerated healing of PRP. It combines the benefit of autologous conditioned serum (ACS) with PRP in a simple 10-minute exercise.
1 Stem Cell Basics: Introduction . In Stem Cell Information [World Wide Web site]. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2009 [cited Monday, March 30, 2009] Available at http://stemcells.nih.gov/info/basics/basics1
2 Becker AJ, McCulloch EA, Till JE (1963). Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197: 452-4.
3 Siminovitch L, McCulloch EA, Till JE (1963). The distribution of colony-forming cells among spleen colonies. Journal of Cellular and Comparative Physiology 62: 327-36.
4 Filip S, English D and Mokry J (2004). Issues in stem cell plasticity. J Cell Mol Med 8 (4): 572-577.
5 Filip S, Mokrý J, Hruška I (2003) Adult stem cells and their importance in cell therapy. Folia Biol.(Prague), 49: 9-14.
6 Stem Cell Basics: What are adult stem cells? . In Stem Cell Information [World Wide Web site]. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2008 [cited Thursday, March 30, 2009] Available at http://stemcells.nih.gov/info/basics/basics4
7 Nakagami H, Morishita R, Maeda K, et al. (2006) Adipose Tissue-Derived Stromal Cells as a Novel Option for Regenerative Cell Therapy. J Atheroscler Thromb 13:77-81.
8 Tholpady SS, Llull R, Ogle RC, et al. ((2006) Adipose Tissue: Stem Cells and Beyond. Clin Plastic Surg 33:55-62
9 Stem Cell Basics: What are the similarities and differences between embryonic and adult stem cells? . In Stem Cell Information [World Wide Web site]. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2009 [cited Thursday, March 30, 2009] Available at http://stemcells.nih.gov/info/basics/basics5
10 Protocol and proprietary Cell Preparation and Activation Media developed by Paspaliaris B (2006) AdiStem Ltd., Hong Kong