In general, human tissues have a very limited potential to regenerate. However, recent progress in stem cell research and tissue engineering promises novel prospects for tissue regeneration in the nearest future. The 21st Century is a century of biomedicine, cell biology, molecular medicine and stem cells.
Diseased, degenerating or damaged organs and tissues give rise to a wide range of chronic illnesses. Patients suffering from such illnesses are currently faced with a relatively short list of options including:
- Long-term drug therapy, which may allow a disease to be managed but rarely cured
- Organ transplant, which there is a shortage of
- Medical devices such as pacemakers
Stem cell research offers enormous potential for major advances in clinical therapy and could be used to replace missing or damaged cells in important diseases (2). Stem cells offer the possibility of a renewable source of replacement cells and tissues to treat life-threatening diseases including genetic disorder, cancer, cardiovascular disease, Parkinson’s disease, Alzheimer’s disease, spinal cord injury, stroke, burns, diabetes, osteoarthritis and rheumatoid arthritis (Table 1).
TABLE 1. Potential US Populations for Stem Cell-Based Therapies
The conditions listed below occur in many forms and thus not every person with these diseases could potentially benefit from stem cell-based therapies. Nonetheless, the widespread incidence of these conditions suggests that stem cell research could help millions of patients.
What are Stem Cells?
The term “stem cell” was proposed for scientific use and has three defining features on which all can agree. (4).
- A stem cell “self-renews”. When a stem cell is called into action, it undergoes cell division. One daughter cell remains a stem cell, while the other becomes more committed to forming a particular cell type by a process called “asymmetric division”.
- A stem cell forms multiple cell types, making it multi-potent.
- A single stem cell completely re-forms a particular tissue when it is transplanted within the body.
Prospective Clinical Applications of Different Stem Cells
Embryonic Stem Cells (ES) refer to the cells of the inner cell mass of the blastocyst during embryonic development (Figure 1). ES are particularly notable for their ability to differentiate into any cell type in the body and the ability to self replicate for numerous generations (5).
Figure 1. Stem cells derived from the inner cell mass of blastocyst stage human embryos have been shown to differentiate into several different cell types and have the potential to one day replace or regenerate tissues. (Source: Krebsbach PH, Robey PG. Dental and skeletal stem cells: potential cellular therapeutics for craniofacial regeneration. J Dent Educ. 2002 Jun; 66(6):766-73).
However, at least two large obstacles stand in the way of this goal. The first technical hurdle is difficulty in manipulating the cells to reproducibly and predictably differentiate into the desired tissue, and no other, clearly indicates the many basic questions regarding the biology of stem cells that must be answered.
Another equally challenging question that must be resolved is one of the law and ethics of stem cell technologies. To date, little attempt has been made towards the use of ES in dental, oral and craniofacial regeneration (6).
Amniotic Fluid-Derived Stem Cells (AFS) can be isolated from aspirates of amniocentesis during genetic screening. While the potential therapeutic value of AFS remains to be discovered, an increasing number of studies have demonstrated that AFS have the capacity for remarkable proliferation and differentiation into multiple lineages, such as chondrocytes, adipocytes, osteoblasts, myocytes, endothelial cells, neuron-like cells and live cells (7).
Umbilical Cord Stem Cells (UCS) derive from the blood of the umbilical cord and there is growing interest in their capacity for self-replication and multi-lineage differentiation (8). UCS have been differentiated into several cell types, such as cells of the liver, skeletal muscle, neural tissue and immune cells.
Although UCS are viewed as neither embryonic stem cells nor adult stem cells, their high capacity for multi-lineage differentiation is likely attributed to the possibility that UCS are chronologically closer derivatives of embryonic stem cells than adult stem cells.
Bone Marrow-Derived Mesenchymal Stem Cells can self-replicate and have been differentiated, under experimental conditions, into osteoblasts, chondrocytes, myoblasts, adipocytes and other cell types, such as neuron-like cells, pancreatic islet beta cells, etc.
When bone marrow is aspirated and cultured, a subset of adherent and mononuclear cells are mesenchymal stem cells (MSCs). To date, the majority of work in this area has focused on the ability of bone marrow-derived MSCs to differentiate into bone. Thus, in vitro expanded bone marrow-derived MSCs may be a rich source of osteogenic progenitor cells that are capable of promoting the repair or regeneration of skeletal defects (Figure 2).
Figure 2. Adult stem cells can be harvested from the bone marrow and expanded in the laboratory. When loaded onto appropriate scaffolds and transplanted back into a deficient site, stem cells have the potential to regenerate bone structures. (Source: Krebsbach PH, Robey PG. Dental and skeletal stem cells: potential cellular therapeutics for craniofacial regeneration. J Dent Educ. 2002 Jun; 66(6):766-73).
Although bone marrow-derived MSCs are inherently heterogeneous, the “plasticity” of this population provides unique scientific opportunities for investigating the role of BMSCs in skeletal homeostasis, genetically modifying potential stem cells, and the potential clinical utility of using autogenous cell therapies to increase the rate and extent of bone formation
Tooth-Derived Stem Cells (TS) are isolated from the dental pulp, periodontal ligament ~ including the apical region ~ and other tooth structures (10). Transplanted skeletal or dental stem cells may one day be used to repair craniofacial bone or even repair or regenerate teeth, (Figure 3).
Figure 4. Adult stem cells can be harvested from the dental tissues such as the dental pulp and expanded in the laboratory. When loaded onto appropriate scaffolds and transplanted back into a deficient site, stem cells have the potential to regenerate tooth structures. (Source: Krebsbach PH, Robey PG. Dental and skeletal stem cells: potential cellular therapeutics for craniofacial regeneration. J Dent Educ. 2002 Jun; 66(6):766-73).
Adipose-Derived Stem Cells (AS) are typically isolated from lipectomy or liposuction aspirates. AS have been differentiated into adipocytes, chondrocytes, myocytes, neuronal and osteoblast lineages. AS can self-replicate for many passages without losing the ability to further differentiate, however, the ability to reconstitute tissues and organs by AS versus other adult stem cells has yet to be comprehensively documented (11).
A great deal of progress has been made in a relatively short time as researchers and clinicians throughout the world are exploring the promise of stem cell transplants for patients with debilitating diseases and degenerative conditions. Despite all enthusiasm about the discovery of stem cells and their great potential, there also is no doubt that in many cases, the applications of and the cures related to stem cells are not just around the corner, as media would lead one to think.
About the Author
Dr. Enes Hodzic graduated from the Dentistry Faculty in Belgrade in 1971. He specialized in Maxillofacial Surgery at Military Medical Academy of Belgrade where he also gained experience in plastic surgery. In 1986 he was trained in the plastic surgery ward at Rikshospitalet University Hospital in Oslo, Norway. After returning from Oslo he worked in Mostar’s hospital as a maxillofacial surgeon. Dr. Hodzic opened the Private Dental Policlynic dr. Hodžić in Metković and its subsidiary in Rovinj and In 2009 he founded the Center for Regenerative Medicine in Rovinj. You may reach him by email at dr.eneshodzic@yahoo.com and his website www.poliklinika-dr-hodzic.com.
REFERENCES
1. Virchow R. Die Cellularpathologie in ihrer Begründung auf physiol. und pathol. Gewebslehre. 1858.
2. Perry D. Patients’ voices: the powerful sound in the stem cell debate. Science 2000; 287:1423.
3. Maximov A. Ueber experimentelle Erzeugung von Knochenmarkgewebe.
Anat Anz 1906; 28:609–12.
4. Lakshmipathy U, Verfaillie C. Stem cell plasticity. Blood Rev 2005; 19(1):29-38.
5. McCloskey KE, Lyons I, Rao RR, Stice SL, Nerem RM. Purified and proliferating endothelial cells derived and expanded in vitro from embryonic stem cells. Endothelium. 2003; 10(6):329-36.
6. Krebsbach PH, Robey PG. Dental and skeletal stem cells: potential cellular therapeutics for craniofacial regeneration. J Dent Educ. 2002 Jun; 66(6):766-73.
7. Prusa AR, Hengstschlager M. Amniotic fluid cells and human stem cell research: a new connection. Med Sci Monit 2002; 8:RA253-257.
8. Laughlin MJ, Barker J, Bambach B, et al. Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med 2001; 344:1815-1822.
9. Alhadlaq A., Mao J.J. Mesenchymal stem cells: isolation and therapeutics. Stem Cells Dev 2004. 13, 436–448
10. Marion NW, Mao J.J. Mesenchymal stem cells and tissue engineering.
Methods Enzymol 2006.420:339-361.
11. Moseley TA, Zhu M, Hedrick MH. Adipose-derived stem and progenitor cells as fillers in plastic and reconstructive surgery. Plast Reconstr Surg. 2006. 118:121-128.
