What is Regenerative Medicine?
Regenerative medicine is a newly emerging branch of modern medicine that refers to the process of replacing or regenerating cells, tissues, or organs to perform their normal functions. Cell therapy; It works by stimulating the body’s own repair mechanism to heal irreparable tissues or organs. Therefore, it may play a role in treating diseases that have no proven treatments or cures yet, such as neurological disorders (spinal cord injury, cerebral palsy, muscular dystrophy, cerebral palsy, Alzheimer’s disease, multiple sclerosis, autism, etc.). It is obvious that stem cell therapies will have a wide place in the treatment of diabetes, cartilage disorders (calcification), waist and neck hernias, cardiovascular diseases, bone diseases, sports injuries, hematopoietic diseases, cancers, hepatic, kidney and dermatological diseases. These revolutionary developments in medicine are expected to be at the forefront of the procedures performed to activate and support the body’s natural healing in the coming years.
one. What is Stem Cell?
Stem cells are unspecialized cells that have the capacity to multiply into any specific cell type of the body, therefore they are smart cells that can transform into the required cell type according to the signal they receive. One cell type originates from another and hence the term “stem cell” is used. It has the ability to transform into various other cell types in the human body. It has two important features.
· Self Renewal: ability to divide indefinitely in cells while maintaining their undifferentiated state,
· potency : Being able to transform into different cell types in cells according to the type of signal they receive. That is, they are parent cells.
Stem cells can be classified into three broad categories based on their differentiation ability. Totipotent stem cells are only found in early embryos. Each cell can form a complete organism. Pluripotent stem cells can form any of the more than 200 different cell types found in the body. that is, they can regenerate an entire organ. Multipotent cells; They are cells that can transform into certain cell types.
2. Different Types of Stem Cells
Stem cells are classified as embryonic stem cells, umbilical cord stem cells and adult stem cells.
Adult Stem Cells:
Adult stem cells are found in most organs of the human body and have different properties depending on their origin. Liver, bone marrow, adipose tissue, brain, etc. They are found in several different tissues. These cells are versatile and can develop into many different cell types. The primary role of these cells is to initiate the repair process in the organ following an injury. Unlike embryonic stem cells, the use of adult stem cells is not considered controversial and does not have ethical issues, as they are derived from adult tissue samples rather than human embryos.
Umbilical Cord Stem Cells:
Umbilical cord blood stem cells are obtained from the umbilical cord immediately after birth. These cells are also called neonatal stem cells and are less mature than stem cells found in the bone marrow of adults or children. It is a rich source of hematopoietic and mesodermal stem cells. It includes endothelial cells, mesenchymal cells, among others. The advantages of using cord blood stem cells are that they can be produced non-invasively, are abundantly available, and graft-versus-host disease is not seen. Cord blood is collected in various countries of the world and stored in public banks for general use or in private cord blood banks by private companies. In addition, the matrix cells of the umbilical cord (Wharton gel) are very rich in terms of mesenchymal stem cells.
Embryonic stem cells:
Embryonic stem cells are derived from an early stage embryo (5-7 days), known as the blastocyst stage, obtained from IVF clinics. Their most notable feature is cells capable of producing all functional adult cell types. In addition to the ability to divide indefinitely, these cells have the ability to differentiate / transform in all fetal and adult stem cells and their mature forms. The presence of these cells makes them useful for cell transplantation, which can be applied to a wide variety of human diseases. However, these cells also have a tendency to form tumors called teratomas, which is their biggest drawback. Currently, therefore, the use of these cells is limited to research only.
Adult stem cells are currently the most practical and viable option for many diseases and can be easily obtained from the same patient.
3. Benefits of Adult Stem Cells
Adult stem cells:
They are abundant and can be easily isolated.
There is no immunological rejection problem.
Adult stem cells have the potential to replace specialized cells in tissue.
There are no ethical issues.
4. Where are adult stem cells found?
I. Bone marrow
Bone marrow is the most accessible and most studied source of adult stem cells. Different types of stem cells have been found in the bone marrow that differ in their potential for cell differentiation and differentiation from one or more germ layers. Contains hematopoietic and mesenchymal stem cells. They have a high ability to transform into other cell types and are versatile. They can be differentiated into many cell types both in vitro and in vivo. Bone marrow cells have been reported to contribute to angiogenesis, somatic muscle development, liver regeneration and the formation of central nervous system cells.
ii. Intestinal stem cells:
The gastrointestinal epithelium is constantly and rapidly renewed throughout life. Therefore, differentiation exists in certain areas of the system. Epithelial cell regeneration in the intestine is provided by multipotent stem cells.
iii. Bone and cartilage stem cells:
Mesenchymal Stem Cell; Under favorable conditions in the bone marrow, it can differentiate into bone and cartilage. If bone or cartilage is damaged, there are stem cells present in the bone or cartilage to participate in the repair process. When the bone is fractured, there is profuse bleeding in the marrow space, which creates a good repair potential with hematoma formation in the marrow area. In cartilage injury, stem cells participate in the repair process. However, these are few in number and regulatory factors are limited. It is thought that these cells can be obtained from surrounding tissues such as muscle, bone or other non-cartilaginous tissues.
iv. Epidermal stem cells (skin and hair):
Human skin consists of outer epidermis and inner dermis. Hair and sebaceous glands also make up the epidermis. The epidermis houses the stem cells at the base of the hair follicle, and its self-renewing properties enable the regrowth of constantly formed hair and skin cells.
v. Nerve stem cells:
Neural stem cells are found in the adult brain. Alternatively, sources of neural stem cells are olfactory mucosa cells, skin, adipose tissue, Schwann cells, etc. It is now a known fact that neural stem cells have the potential to treat incurable neurological disorders.
5. Benefits of using Bone Marrow Derived Mononuclear Cells (BMMNCs):
Bone marrow derived stem cells are one of the oldest sources and are widely used for blood diseases/disorders.
Sibling/allogeneic (related/matched donors) bone marrow transplantation for leukemia, thalassemia, sickle cell anemia has been used as standard medical practice for over 150 years. Stem cells can be obtained from bone marrow very easily. It has been widely studied and researched. Bone marrow consists of various cell fractions, each with its own function and role. These fractions are hematopoietic stem cells, mesenchymal or stromal stem cells, very small embryonic stem cells, endothelial stem cells. Because each of these has a different function, a cocktail of these cells has a combining effect and is therefore more effective than infusion or transplant of a single type of cell (eg Mesenchymal stem cell only).
a) Hemopoietic stem cells: Bone marrow is rich in these stem cells, which stimulate the formation of new blood vessels, secrete chemicals suitable for repair and regeneration, and support functional and metabolic development.
b) Mesenchymal stem cells (Multipoint Mesenchymal Stromal Cells): These are multicomponent cells with the potential to differentiate into multiple lineages, including bone, cartilage, muscle, tendon, ligament fat, nervous tissue or brain tissue and various other connective tissues. They also contribute to angiogenesis, somatic muscle development, liver regeneration, and formation of central nervous system cell types.
c) Multipolar Adult Progenitor Cells (MAPC) d) Marrow Isolated Adult Multistage Inducible (MIAMI) Cells
d) Multipolar Adult Stem Cells (MACS) and
e) Very Small Embryonic-Like (VSEL) Stem Cells: They contribute more to the efficacy of bone marrow derived cells and are considered pluripotent (can form a wide variety of cell types).
How do stem cells work?
Stem cells are actively involved in the formation of new tissues, thereby promoting repair and regeneration. When injected, these cells migrate to damaged areas of the tissue due to the release of chemical signals and fuse with these tissues and aid regeneration. The functioning mechanisms demonstrated by stem cells can be noted as follows:
Homing: Once injected into stem cells, they have a unique ability to “homing” or migrating to the injury site to perform the repair process.
Transdifferentiation: These cells can multiply and form cells of the same tissue or form cells of a completely different tissue. Cells differentiate independently or by fusing with resident cells.
Paracrine activity: stem cells produce a variety of chemical factors that activate resident cells and stimulate them to repair damaged tissue.
Increased angiogenesis: stem cells help in the creation of new blood vessels. This increases blood circulation and oxygen supply throughout the body. This happens as cells differentiate and form new tissues, or by paracrine activity that indirectly increases angiogenesis.
Immune regulation: stem cells release factors that regulate the affected immune system and reduce inflammation.