1Stem Cells
Content
Ulternative Therapy
Dental Pulp Stem Cells,
a New Era in Tissue Engineering Abstract Stem cells are primitive cells that can differentiate and regenerate deteriorating cells in different parts of the body such as heart, bones, muscles and nervous system. For years scientists all over the world have been working on possibilities of using these stem cells to regenerate human cells which are damaged due to illness, developmental defects and accidents. This article is to give an overall idea about stem cells in general, history and future, and where does dentistry stand in that field.
Key words: Stem cell, Embryonic stem cells, Adult stem cells, SHED, Chondrocytes, Osteoblasts, Adipocytes, Mesenchymal stem cells.
Introduction
Dr. Ghada A. Karien BDS, JDB (Paed) • Paediatr Paediatric ic dentist Jordanian Dental Board in paediatric dentistry • MOH/Al-Basheer hospital [email protected]
The term stem cell was proposed proposed for scientific use use by Russian histologist A Alexander lexander Maksimov in 1908. While research on stem cells grew out of findings by Canadian scientists in the 1960s. 1, 2 In general there are two broad types of stem cells which are: Embryonic stem cells, and Adult stem cells. Embryonic stem cells were harvested from embryos, they are cells derived from the inner cell mass of the blastocyst (early stage embryo, 4-5 days old, consist of 50-150 cells) of earlier morula stage embryo.3 In other words these are the cells that form the three germ layers, and are capable of developing more than 200 cell types. t ypes. In 1998 the first human embryonic stem cell line was derived at university of Wisconsin-Madison.4 Embryonic stem cells have both moral and technical problems, because these cells will later develop into a human being, taking these cells will require destruction of an embryo. Technically Technically these cells are difficult to ccontrol ontrol and grow and and they might as well form tumors after their injection. Differentiating embryonic stem cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic embryonic stem cell researchers still fa face. ce.5 And after ten years of research6, there are no approved treatments or human trials using embryonic stem cells; but because of the combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain theoretically potential source of regenerative medicine and tissue replacement after injury ora disease.
6
Smile Dental Journal Volume 4, 4, Issue Issue 2 - 2009
Tissue engineering and regenerative regenerative medicine seek to replace lost or damaged tissues due to any reason, and this needs three major ingredients which are: 1- Morphogenic signals such as growth factors and differentiation factors, these factors play an important role in the multiplication and differentiation of stem cells into the specifically needed type of cells.
blindness, multiple sclerosis, muscle damage and many other diseases.14,15,16,17 Specifically talking about the dental field, years from now dental stem cells will hopefully be able to correct cleft palate sparing children from multiple surgeries, stem cells will also have the potential to save injured teeth and jaw bones, correct periodontal defects, and most strikingly regenerating entire teeth structures is the horizon.
BMPs (bone morphogenic proteins) and cytokines play a major role in organogenesis, and in the dental aspect specifically GDf-11 (growth/dierentiation (growth/dierentiation factor 11) which is a novel member of BMP/TGF B family is expressed in dierentiating odontoblasts and plays a major role in differentiation of dental pulp stem cells into odontoblasts which is the corner stone in teeth tissue engineering.13 22- Responding Responding stem cells which are originally harvested from the patient and preserved under good conditions to maintain their special ability to differentiate into a wide range of cells. 33- Scaffold Scaffold of extra cellular matrix, which provide these cells with the environment and mold to grow into what we want them to become and function.
Many people will ask themselves, how can the scientists be able to use dental stem cells in regenerating dental tissues?
Well, there are three approaches which were investigated by different labs to implant stem cells from teeth in humans and these are: 1- Placing the stem cell into a mold of tooth crown which is made of Enamel-like substance with a scaffold material, and then they will start star t to loop blood vessels through this scaffold, after that this will be implanted elsewhere in the body and wait until it is mature, then these teeth will be extracted and implanted in the oral cavity. 22- Harvesting Harvesting a wisdom tooth of a person and releasing stem
One thehis major one using gets from cells of from ownadvantages body and then themharvesting later in hisstem tissue regeneration if he has an illness is that there will be no refusal of these cells as they are already body parts, in other words the patient will not need to go through the process of immunosuppressant immunosuppressa nt and that will spare him lots of suffering and time. In the future, f uture, medical researchers anticipate being able to use technologies derived from stem cell research to treat a wider variety variet y of diseases including cancer, Parkinson’s, Alzhimer, spinal cord injuries, diabetes, heart diseases, liver disease,
cells from their pulp tissue, stem cells are then a severely injured tooth, forthe example in cases of carimplanted accidents in or falling down, and these implanted stem cells will help to regenerate the pulp of the injured teeth sparing them root canal treatments. 3- If there are no teeth present in the oral cavity from which stem cells can be harvested, we can take stem cell from unerupted wisdom tooth, organize them into three dimensional structures and give proper cues to them before putting them back into the socket; this is like planting a seed and waiting for it to grow.18 Discovery that human mature pulp tissue contains a population of multi-potent mesenchymal dental pulp stem cells with high proliferative proliferativ e potential for self renewal and the ability to differentiate into functional odontoblast has revolutionized dental research and opened new avenues in particular par ticular for reparative and reconstructive dentistry and tissue engineering in general. Stem cell therapy which was once a science fiction is now becoming more towards reality, and it might make the dream of many people come true. So parents taking the decision to bank their children’s children’s milk teeth might be the best gift they could ever give to their child. Milk teeth which were kept by children under their pillows to be collected by the tooth fairy might have a greater meaning; the tooth fairy might be able one day to save their life.
8
Smile Dental Journal Volume 4, Issue 2 - 2009
Ulternative Therapy
That opened the window wide for for the so called adult stem cells, which are cells found in a developed organism and they have two properties: first the ability to divide and create another cell like itself. Second they divide to create a more differentiated cell than itself. They can be found in both children and adult.7 Adult stem cells can in general be found in umbilical cord blood, blood and bone marrow. Pluripotent stem cells can be found in cord blood but are small in Number Number..8 These adult stem cells have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants. The first one marrow transplant between two siblings was done successfully in 1968.
Osteoblasts: They They are stem cells that have have the ability to Osteoblasts: regenerate bone. Adipocytes: Another type of stem cells that have the ability to repair damaged cardiac tissues following a heart attack. Mesenchymal Stem Cells: Those among Cells: Those are the most potent among all tissue stem cells and have the ability to differentiate into various types of reparative cells. In general Mesenchymal Stem Cells MSC are non-haematopoietic stromal cells capable of differentiating into a range of cells, those cells were first discovered in bone marrow and they were noticed to have the ability to double into many populations without loss of function, they also have the so called homing property which means that when they are delivered systemically they migrate to the site of injury. injur y. So it is to say that MSC are more promising for therapeutic applications than other types of stem cells. 12
Most adult stem cells are lineage restricted and are generally referred by their tissue of origin e.g. mesenchymal stem cells, adipose derived stem cells, endothelial stem cells...etc.9,10
Stem Cells in Dentistry In the year 2003 Dr. Songtao Shi who is a paediatric dentist discovered baby tooth stem cells by using the deciduous teeth of his six year old daughter, he was luckily able to isolate, grow and preserve these stem cells’ regenerative regenerative ability, and he named them as SHED (Stem cells from Human Exfoliated Deciduous teeth).11 After the scientists studied the dental pulp looking for stem cells they found that the dental pulp was rich in different stem cell types such as: Chondrocytes: Chondrocytes: which which are stem cells that have the ability to regenerate cartilage and these cells play an important role in the treatment of arthritis and joint diseases.
Mesenchymal stem cells
Recently stem cell banks are present, and even some of these banks do not only freeze cord stem cells but also dental stem cells of baby teeth. This can be done easily when a child’s anterior milk tooth is shedding, the tooth is extracted by the dentist and preserved inthen a special kit provided from the stem cell bank company who in their turn transfer the tooth to their special labs to harvest the dental stem cells and store them in their bank for each child confidentially until they are needed later for the child himself or a member of his family. Smile Dental Journal Volume 4, Issue 2 - 2009
7
Ulternative Therapy
Refrences 1. BECKER AJ, McCULLOCH EA, TILL JE. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature. 1963 Feb 2;197:452-4. 2. SIMINOVITCH L, MCCULLOCH EA, TILL JE. The distribution of colony-Forming cells among spleen colonies. J Cell Physiol. 1963 Dec;62:327-36. 3. Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science. 1998 Nov 6;282(5391):1145-7. 4. “New Stem-Cell Procedure Doesn’t Harm Embryos, Company Claims”. Fox News. http://www.foxnews.com/story/0,2933,210078,00.html. 5. Wu DC, Boyd AS, Wood KJ. Embryonic stem cell transplantation: potential applicability in cell replacement therapy and regenerative medicine. Front Biosci. 2007 May 1;12:4525-35. 6. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science. 1998 Nov 6;282(5391):1145-7. 7. JJiang Y, Jahagirdar BN, Reinhardt RL, et al. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002 Jul 4;418(6893):41-9. Epub 2002 Jun 20. 8. Ratajczak MZ, Machalinski B, Wojakowski W, Ratajczak J, Kucia M. A hypothesis for an embryonic origin of pluripotent Oct-4(+) stem cells in adult bone marrow and other tissues. Leukemia. 2007 May;21(5):860-7. Epub 2007 Mar 8. 9. Barrilleaux B, Phinney DG, Prockop DJ, O’Connor KC. Review: ex vivo engineering of living tissues with adult stem cells. Tissue Eng. 2006 Nov;12(11):3007-19. 10. Gimble JM, Katz AJ, Bunnell BA. Adipose-derived stem cells for regenerative medicine. Circ Res. 2007 May 11;100(9):1249-60. 11. Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, Shi S. SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A. 2003 May 13;100(10):5807-12. Epub 2003 Apr 25. 12. Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells. 2007 Nov;25(11):2739-49. Epub 2007 Jul 26. 13. Nakashima M, Mizunuma K, Murakami T, Akamine A. Induction of dental pulp stem cell differentiation into odontoblasts by electroporation-mediated gene delivery of growth/dierentiation factor 11 (Gdf11). Gene Ther. 2002 Jun;9(12):814-8. 14. Fiegel HC, Lange C, Kneser U, Lambrecht W, Zander AR, Rogiers X, Kluth D. Fetal and adult liver stem cells for liver regeneration and tissue engineering. J Cell Mol Med. 2006 Jul-Sep;10(3):577-87. 15. Timper K, Seboek D, Eberhardt M, Linscheid P, Christ-Crain M, Keller U, Müller B, Zulewski H. Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells. Biochem Biophys Res Commun. 2006 Mar 24;341(4):1135-40. Epub 2006 Jan 26. 16. Lindvall O. Stem cells for cell therapy in Parkinson’s disease. Pharmacol Res. 2003 Apr;47(4):279-87. 17. Goldman SA, Windrem MS. Cell replacement therapy in neurological disease. Philos Tra Trans ns R Soc Soc Lo Lond nd B Biol Biol Sc Sci.i. 20 2006 06 Sep 29 29;3 ;361 61(1 (147 473) 3):1 :146 4633-75 75.. 18. Zhang W, Walboomers XF, van Kuppevelt TH, Daamen WF, Bian Z, Jansen JA. The performance of human dental pulp stem cells on different three-dimensional scaffold materials. Biomaterials. 2006 Nov;27(33):5658-68. Epub 2006 Aug 17.
