Science and Technology

Definitions And Frequently-Asked Questions
What are Stem Cells?
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

Research by Canadian scientists Ernest A. McCulloch and James E. Till in the 1960s saw the beginning of stem cell research. 2, 3

 Stem Calls
Fig.1: Stem cell division and
Differentiation
A - stem cell
B - progenitor cell
C - differentiated cell
1 - symmetric stem cell division
2 - asymmetric stem cell division
3 - progenitor division
4 - terminal differentiation
Source: Wikepedia - Self-built
Author: User:Wykis
Permission: Public Domain
What are Embryonic Stem Cells?
Embryonic stem cells are cells which form an inner cell mass at the 4-5 day (Blastocyst) stage of human embryo development. They are responsible for the development of a human embryo into a human fetus by giving rise to specialized embryonic tissues. Embryonic stem cells are not present in the adult human and can only be obtained through the destruction of a human embryo.
What are Adult Stem Cells?
Adult stem cells (ASCs) are unspecialized or undifferentiated cells found in children and adult humans. These lie dormant (quiescent) and non-dividing within different adult human tissues until they are activated by signals from diseased, dying or damaged tissue to not only divide to form more stem cells, but also to differentiate into different types of specialized cells to replenish or regenerate these affected cells.

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 Σωματικóς, of the body) stem cells.
What is Stromal Vascular Fraction?
Stromal Vascular Fraction (SVF) is the lipoaspirate obtained from tumescent liposuction minus the fat cells (adipocytes). Apart from adipocytes, the SVF contains a variety of other cells such as pre-adipocytes, endothelial cells, smooth muscle cells, pericytes, fibroblasts, and adult stem cells (ASCs). In addition, the SVF also contains blood cells from the capillaries supplying the fat 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
What are the main advantages of Adult Stem Cells over Embryonic Stem Cells?
Embryonic stem cells can only be obtained by destroying a human embryo. This poses ethical and religious issues. However, there are no ethical issues with the use of ASCs because these cells can be obtained from adult human tissue; for example from liposuctioned adipose tissue (fat). Another important advantage of using ASCs is that these are autologous - one's own cells - which the body will not reject. 9 ASCs from bone marrow have been successfully transplanted in sufferers of leukemia and related cancers for many years now.
What are the sources of ASCs from one's own body?
Adult stem cells are present in all tissues in the human body. The major sources of ASCs that can be obtained from an adult human are:
  1. Bone marrow
  2. Peripheral blood, and
  3. Adipose Tissue (Fat).
Which is the best source to harvest ASCs from the human body?
The best source to harvest ASCs from one’s body is the adipose tissue. Below is a comparison of three sources:
  • Bone marrow - About 50,000 ASCs can be harvested at any one time. These mostly become blood cells.
  • Peripheral blood - About 10,000 ASCs can be harvested at any one time. 50% of which will become blood cells and 50% will become tissue cells.
  • Adipose tissue (Fat) - About 10 to 50 million stem cells can be harvested at any one time, 5% of which will become blood cells and 95% will become tissue cells.
Why is Adipose tissue the best source for harvesting ASCs?
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.
What is Autologous Adipose-derived Adult Stem Cell Transplant?
It is, in this case, a four hour outpatient procedure. 10 It involves the following:
  1. Harvest: Using a proprietary but simple procedure similar to tumescent liposuction, 100cc of adipose tissue is harvested from the patient.
    In some cases, an additional 300cc of adipose tissue is harvested for up to THREE follow-up treatments. See item number 9 below on stem cell banking.
  2. Breakdown: The adipose tissue is then broken down using a combination of Collagenase Type 1 Solution, and a proprietary Cell Preparation Medium.
  3. Separate: Using standard techniques, the Stromal Vascular Fraction (SVF) which contains Adult Stem Cells (ASCs) is separated from the fat cells.
  4. Isolate: ASCs and other progenitor cells are then isolated from the SVF using standard techniques.
  5. Wash: The cells are then triple-washed with saline to remove any traces of the collagenase and cell preparation medium.
  6. Activate: The isolated ASCs are then suspended in the person's own platelet-rich-plasma (PRP) growth factors and activated with AdiStem's red/yellow/green laser. This 'awakens' or activates the dormant ASCs.
  7. Label: The stem cells are incorporated with a radionuclide label prior to administration to help track stem cells by conventional gamma and SPECT scans.
  8. Infuse: The cells are then administered back to the patient through one or more of the following modes of administration:
    1. Intravenous: The ASCs are administered through a standard intravenous drip
    2. Fat Transfer: The ASCs are mixed with the fat filler-biomaterial mix before reintroduction, and
    3. Topical: The ASCs are administered directly into a localized area different from their tissue of origin.
  9. Bank: Banking of stem cells is imperative for some procedures that require repeat administration. This is done under EU GMP protocol.
References

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
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