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Stem Cells and Tissue Regeneration

Authors : Dr. Ivona .

Introduction

Regenerative medicine is a multidisciplinary field that seeks to develop functional cell tissues,organ substitutes to repair ,replace ,enhance

  • biological functions that have been lost due to
  • congenital abnormalities
  • injury
  • disease
  • aging (National Institute Of Health USA).regenerative medicine has two different principals of action-Growth factors and stem cells.

Growth Factors and all the cascade of regenerative events which follows starts with collecting of autologous blood and the process is called PRP.The other more potent rejuvenation potential lies in stem cells.

Stem cells are immature, unspecialized cells that have the potential to develop into many different cell lineages through their natural potential of differentiation. By the conventional definition, these cells can renew themselves indefinitely through “self-renewal”, and they vary in terms of their location in the body and the type of cells that they can produce. Recent studies have revealed that the oral tissues, which are easily accessible for dentists, are a rich source of stem cells.

In facial rejuvenation we do use adipose derived stem cells. The best quality of adipose derived stem cells are their easy harvesting, good quantity and yield which doesn’t require multiplying in vitro.

Given their unique abilities, stem cells are particularly important for developing innovative technologies for tissue engineering strategies to regenerate or replace damaged, diseased or missing tissues and even organs by in vitro cell manipulation and design of the extracellular environment.

Stem cells are found in all multicellular organisms.They divide by mitosis and are characterized by the power of self-renewal and the capacity of differentiation or conversion into specialized cells of tissues and organs. When they are sent to an injured spot in the body and exposed to a bodie’s given signal, stem cells convert into cells of the tissue or organ that is injured.

Stem cells are, therefore, like a small army in our organism that preserves and regenerates each of its corners. If the signalling system within the stem cells is disrupted or their number is insufficient, or else their division and/or differentiation is not possible, no recovery from the respective disease or infection occurs.

Stem cells can have double origin. They can be of embryonic origin (can be extracted from the inner cell mass of the blastocyst - an embryo), in which case their division is difficult to control. They are also the subject of much ethical debate (the extraction of stem cells usually destroys the blastocyst), so they are not used in treatment . These are the only totipotent cells and can differentiate into absolutely any cellular type, as well as into the placental tissue.

Adult stem cells are found in all organs of mammals, where they are active in the process of self-healing or self-regeneration of tissues and organs, with no observed malignant transformations. They are pluripotent and can differentiate into any cell of an adult organism.

They are most readily sequenced from the bone marrow, the fat tissue of the abdomen and groin, and from the umbilicus.

Bone marrow stem cells can be haematopoetic (they are transforming into blood cells with a differenttiation impulse) or mesenchymal-they can differentiate and form bone, cartilage, ligaments, tendons, etc. . In contrast, the stem cells extracted from the adipose tissue are exclusively of mesenchymal origin.

You may wonder how stem cells begin their differentiation and how they know which cell they have to convert (differentiate) into or which tissue needs help.

There are multiple ways in which stem cells start the differentiation in the process of tissue and organ regeneration. Stem cells are subject to signals from the environment, the so-called exterior signals, and to interior signals. Internal signals are controlled by the cellular genome which carries the encoded instructions for all cellular structures and functions. External signals, which lead to the differentiation of stem cells, combine biochemical signals, secreted by cells from the environment (growth factors, antiapoptotic factors, immunosuppressive factors, angiogenic factors, factors of collagen simulation, etc.), by mechanical contact between the neighbouring cells, and certain molecules from the microenvironment in which the cells are located.

Inside the cells, a whole cascade of biochemical signals are activated, which in turn leads to changes within the cell cytoskeleton and in the membrane activity, metabolism and genetic expression. It is in this seeingly simple but in fact very complex way that the differentiation of stem cells begins, which is essential for tissue regeneration.

P 206 Today, stem cell treatment represents a great hope and a kind of revolution in the field of regenerative medicine. The simplest way to substantiate this thesis is by giving an example which will help us to better understand this new and promising field of DNA medicine that the stem cells are opening.

At present, reparation is the only answer that therapeutic medicine has in cases of dysfunction of organs or tissues.

It means briefly,that, when an organ is not performing its function in the human body adequately and is of vital importance, we need to replace it with a new one. For example, myocarditis and heart failure nowdays lead to heart transplantation. The first step is to find a suitable and DNA compatible donor and then transplant the organ, but the recipient (unless the donor and the recipient are identical twins) will have to remain under immunosuppressive treatment for the rest of his/her life.

  • Task
  • Differentiation
  • Tissue
  • Therapeutic implications
  • Chondrogenesis (formation of cartilage)
  • Chondrocytes
  • Cartilage
  • Joint diseases (OCD, OA, rheumatoid diseases, malformations)
  • Osteogenesis (bone formation)
  • Osteocytes
  • Bone
  • Bone fracture and bone diseases
  • Myogenesis (formation of muscle)
  • Myocytes
  • Muscle
  • Muscle disease, myocarditis
  • Tendonogenesis (formation of tendons)
  • Ligamentogenesis (formation of ligaments)
  • T/L fibroblasts
  • Tendon ligament
  • Injury to ligaments and tendons
  • Other
  • Adipocytes, keratinocytes ...
  • Connective tissue
  • Wound healing and other ...

(only if we have donner and hoste being identical twins)p 207. This treatment allows normal functioning of the transplanted organ, but in the long term it also represents a high risk of developing a malignancy, as well as the risk of a variety of other diseases caused by suppression of the immune system.

Imagine what tissue regeneration through the formation of a completely identical organ would mean to such a patient, in our case a patient with a weakened heart function. Such an organ, obtained through differentiation and transformation of stem cells into heart muscle cells, would be identical to his/her own, as if they had got it from their non-existent identical twin sibling. There is no risk of rejection, no immunosuppressive therapy, no immunodeficiency and no threat of developing cancer!

We can therefore rightly claim that the stem cells and their great potentials have opened a new era in medicine and regenerative therapy. There is no doubt that the only true and absolute solution to an vital organ failure lies in its own regeneration with the stem cells!

It is the stem cells that are nowadays the focus of almost all the hopes and expectations for treatments of numerous serious diseases (muscular dystrophy, autism, cerebral palsy, heart disease, multiple sclerosis, cancer, leukaemia, etc.). Many treatment protocols have already been successfully carried out, and some are already in routine practice.

Application of stem cells in dentistry

In dentistry, tissue engineering is also considered to be a new frontier in the regeneration of missing oral tissues, organs and teeth regeneration. For example, various degrees of alveolar bone resorption occur after tooth loss/extraction because of periodontal disease, severe caries, root fractures or accidental trauma.

In addition, the bone resorption in the residual ridge, particularly in the mandible, continues throughout life in many edentulous patients . Therefore, stem cell and tissue engineering therapies are expected to provide a novel capability to regenerate large defects in periodontal tissues and alveolar bone and, and to ultimately replace the lost tooth itself. The tissues and organs targeted for such regenerative medicine strategies in dentistry include the salivary gland tongue and craniofacial skeletal muscles , as well as the condylar cartilage of the temporomandibular joint .

The big source of regeneration is lying in teeth, itself. They do contain pulp stem cells, periodontal stem cells in periodontal ligament itself.

Huge hopes do lie into the milky teeth and their stem cells with huge potential of differentiation.

The impacted molars are the valuable source of stem cells too.

Sources of adult stem cells in the oral region.

  • BMSCs: bone marrow-derived stem cell
  • DPSCs: dental pulp stem cells
  • SHED: stem cells from human exfoliated deciduous teeth
  • PDLSCs: periodontal ligament stem cells
  • DFSCs: dental follicle stem cells
  • TGPCs: tooth germ progenitor cells
  • SCAP: stem cells from the apical papilla
  • OESCs: oral epithelial progenitor/stem cells
  • PSCs: periosteum-derived stem cells
  • SGSCs: salivary gland-derived stem cells

Application of Adipose Stem Cells in Anti-Ageing Medicine And face rejuvanation

Stem cells have found wide application in regenerative therapies but also another large field of medicine - anti-ageing medicine is more than welcoming stem cell therapies. In ageing, the number of stem cells decreases, as do their signaling potentials and due to that regeneration of various organs and tissues in our bodies.. When we are young, stem cells regenerate the lung parenchyma in smokers, or they regenerate skin burns from the sun, but with ageing, the tissue regeneration gradually weakens. If we simply increase the number of stem cells in circulation via intravenous injections , we have already done something that may trigger faster and stronger responses in tissue reparation. This method of increasing the stem cells number is a preventive method in anti-ageing medicine used as a powerful booster of our immunity system .

For the treatment of facial rejuvenation, we mostly use the therapy known as stem-cell facelift, performed by using combining stem cell and PRP method, and power cell facelift (scaffold facelift), facelift obtained using stem cells, the PRP method and threads which form the basis around which tissue regeneration takes place.

There are two ways in which stem cells are obtained (extracted) for stem cell facelifts.

One way is to extract them from the adipose tissue of the groin and the abdomen, and the other is by induction from the bone marrow. We use autologous transplants of stem cells from the abdominal adipose tissue because this is a completely natural and minimally invasive procedure carrying the less possible side effects. The gently extracted stem cells, also called fresh stem cells, are returned to the donor's body within four hours of extraction.

Therefore, there is no risk of contamination and no external manipulation of stem cells, such as encountered in their laboratory reproduction. Once the adipose tissue with stem cells has been collected in the non-aggressive manner, like in liposuction, stem cells are isolated from the fat by centrifugation and then mixed with the patient's PRP (platelet rich plasma), obtained from 15 ml of the patient's blood. In this way we obtain an autologous transplant of growth factors and cytokines, which stimulate tissue regeneration and perfectly combines with the centrifuged stem cells. Everything that is obtained in this manner is the patient's, autonomous, which is why we speak about autologous stem cell transplants enriched by autologous growth factors and stimulants of tissue regeneration.

The order of inserting personal fillers (made from stem cells and prp which are patients autonomus) obtained on the way described above is mainly as follows:

  1. The personal (autologous, individual) subcutaneous or dermal filler is first injected deep around the eye socket to regenerate the subcutaneous layer, under the muscle

  2. In the next phase, the personnel filer is injected on the very surface of the circular eye muscle (M. orbicularis occuli), which results in regeneration of the muscle and the superficial layers of the skin.

  3. The same procedure is used for regeneration of the central part of the face – the cheek area and the nasolabial folds.

  4. The entire procedure is completed by positioning the personnel filler very shallow, close to the surface to achieve regeneration of all layers of the skin and subcutaneous tissues.

It is important to point out that stem cells are placed on the muscles right next to the bone on order to obtain regeneration of all parts of the face.

References

  1. J.M. Slack Origin of stem cells in organogenesis Science, 322 (2008), pp. 1498–1501 View Record in Scopus | Full Text via CrossRef | Citing articles (77)
  2. R. Langer, J.P. Vacanti Tissue engineering Science, 260 (1993), pp. 920–926 View Record in Scopus | Citing articles (5374)
  3. D. Kaigler, D. Mooney Tissue engineering's impact on dentistry J Dent Educ, 65 (2001), pp. 456–462 View Record in Scopus | Citing articles (36)

More references are availabe on request.