**3. Application of stem cells in reconstruction of maxillofacial region and treatment of head and neck pathology**

Stem cells have a wide application including treating variety of diseases and reconstruction of maxillofacial region, head and neck. Stem cells can be broadly classified into embryonic and adult somatic mesenchymal types. Adult stem cells are categorized into bone marrow, adipose tissue and dental sub varieties. Embryonic stem cells are categorized into somatic and pleuripotent stem cells. Both embryonic and adult stem cells can be further classified into undifferentiated, early differentiated and differentiated stem cells. The early differentiated stem cells from both the above types can be used along with the scaffold in the reconstruction of the surgical defect of maxillofacial region.

*Perspective Chapter: Role of Genetics, Stem Cells in Reconstructive Surgery—Their Perspectives… DOI: http://dx.doi.org/10.5772/intechopen.109514*

Bone marrow and adipose derived stem cells have been used along with autogenous bone grafts as scaffold in jaw reconstruction. Stem cells have been found effective in treatment of oral mucosal lesions, malignancies of the craniofacial region, along with auto immune and systemic diseases as well.

Various clinical trials are in vogue presently regarding the effect of stem cells as a treatment modality. This presentation attempted to focus insight into the application of stem cell therapy in treatment of diseases as well as reconstruction of the maxillofacial region.

Stem cells are building blocks of all organs, tissues, blood and immune system that serve as an internal repair and regeneration. Found in blood, bone marrow, muscle, adipose tissue, skin, heart, liver, placenta, amniotic fluid, membrane and sac. They lie dormant until needed to regenerate the diseased tissue. Adult humans have blood creating stem cells in bone marrow ranging between 50,000 to 2,00,000. They are activated to proliferate and differentiate into required type, upon their loss, thus maintain tissue homeostasis. Various types of stem cells are embryonic, adult, mesenchymal, tissue specific, Induced pluripotent stem cells. The adult stem cell types are hematopoetic, mesenchymal, neural, epithelial, adipose.

### **4. Cancer stem cells**

Cancer stem cells arise from normal somatic stem cells. In the process of normal differentiation, a cell differentiates to form two cells, differentiated and primitive. A terminally differentiated cell is formed from precursor progenitor cell and finally undergoes apoptosis. CSC may originate from a normal stem cell, a normal progenitor cell or a normal differentiated cell by genetic mutation which will activate self renewal genes. During the normal differentiation process of the stem cell, instead of apoptosis, mutations occur in stem cell, progenitor cell and differentiated cell, by which they transform into respective mutated cells, there by resulting in formation of a cancer stem cell. The tumor tissue microenvironment is composed of a variety of cells, including tumor cells, cancer stem cells along with blood vessels. The cancer stem cells are rare cells found primarily in the invasive edge of tumors close to blood vessels [6].

Human cancer tissues are heterogeneous in nature and become differentiated during expansion of cancer stem cells (CSCs). CSCs initiate tumorigenesis, and are involved in tumor recurrence and metastasis. Furthermore, data show that CSCs are highly resistant to anticancer drugs. Human cancer tissues are heterogeneous in nature and become differentiated during expansion of cancer stem cells CSCs). CSCs initiate tumorigenesis, and are involved in tumor recurrence and metastasis. Furthermore, data show that CSCs are highly resistant to anticancer drugs [6].

#### **4.1 Therapeutic targeting strategies for CSCs**

Stem cells here play a dual role-in carcinogenesis and in the development of possible new cancer treatment options in future. For past so many years stem cells have been used in the replenishment of blood and immune system damage during treatment of cancer by chemotherapy or radiotherapy. Other than their use in the immuno-reconstitution, the stem cells have been reported to contribute in the tissue regeneration as they have extraordinary capacity to regenerate and differentiate. The MSCs have been used in the cell-based bone reconstruction following chemotherapy and surgery in malignancies like osteosarcoma and Ewing sarcoma [7].

Another important aspect of their use in cancer therapy is the use as delivery vehicle. Systematic delivery of drug or gene therapy has promising future but is currently limited by various factors such as immune detection, nonspecific accumulation in normal tissues and poor permeation. Stem cells can be cell based carriers that target the desired site [7, 8]. Stem cells are also used as delivery vehicles based on the hypothesis that the tumor cells send factors such as Vascular endothelial growth factor, to recruit mesenchymal stem cells from the supporting stroma of the tumor.

New techniques of targeting specific cell membrane growth factor receptors or downstream signaling pathway mutations are currently under investigation, especially in patients with metastatic tumors. One of the most promising strategies for cancer treatment is inhibiting the key self-renewal signaling pathways (e.g. Wnt, SHH, Notch signaling pathways) that are aberrantly active in CSCs, introducing novel therapeutic approaches for HNSCC. These new therapeutic techniques have a significant reduction in the CSCs, reducing its tumorigenicity, apoptotic resistance, and enhanced the sensitivity to Cancer therapy. The markers used to isolate, identify and enrich CSCs such as CD44-HYALURONIC ACID RECEPT0R, CD 24- HEAT STABLE ANTIGEN (for solid tumors), CD133, CD166, Ep CAM etc. are also ideal targets for cancer therapy.

Targeting ATP binding casette transport drugs plus other chemotherapeutic drugs, also offers a very powerful and selective strategy to eliminate CSCs. Recent therapeutic strategies exploited the interdependence of CSCs and vascular endothelial cells (perivascular niche) in head and neck cancer to decrease the rate of tumor recurrence and distant metastasis.

Compounds targeting the intrinsic and extrinsic apoptosis pathways are bicyclic cyclohexenones capable for inhibiting NF-jB signaling by inhibiting NF-jB-induced interleukin-8 (IL-8) expression, thus exerting anti-proliferative activity against lung adenocarcinoma epithelial cell line, T cell lymphoblast-like cell line, and prostate carcinoma cell line.

Nuclear factor kappa-light-chain enhancer of activated B cells (NF-jB) is a transcription factor that inhibits apoptosis by elevating the expression of survival factor. Another interesting way to manage tumor progression is inducing the terminal differentiation of CSCs to lose their self renewal property, by the means of either retinoic acids or drugs targeting tumor epigenetic changes.

#### **4.2 Procurement and delivery of stem cells**

Stem cells can be derived from the following sources like embryonic stem cells sources and adult stem cells sources. The tissue samples containing stem cells are placed under specific conditions in laboratories/stem cell banks. The extraction of these stem cells is possible due to unique receptors like Oct 4, TRA-1-60 Nanog, SSEA4, TRA-1-60 and TRA-1-81 (stem cell markers) present on the stem cell surface [7]. Tissue samples containing stem cells are placed in a sealed vial containing an appropriate media, which nourishes it during transport. The extracted stem cells are grown on a suitable scaffold medium made of biomaterials (biodegradable or non biodegradable) such as poly lactic acid, polyglycolic acid (PGA), polyethylene terepthalate, polypropylene fumarate, hydroxyapatite/tricalcium phosphate, fibrin, alginates, and collagen polytetrafluoro ethylene, fibrin sealent and certain growth factors that act as matrix during regeneration of the tissue. Stem cells are loaded in an suitable carrier called "scaffold" for transfer to desired site to close the defects or replace the organ. Scaffold can be of different shapes, pattern and biomaterials.

*Perspective Chapter: Role of Genetics, Stem Cells in Reconstructive Surgery—Their Perspectives… DOI: http://dx.doi.org/10.5772/intechopen.109514*

The sample should reach the processing storage facility before 40 hours. In the laboratory the samples were trypsinized and passaged to yield colonies of stem cells. The required cell type can be manipulated by utilizing right inductive signals and appropriate growth factors to the stem cells. Cultured stem cells should be passed through stem cell markers before it is administered to patients to know the lineage of the cell. Endotoxin test should be subjected compulsorily to the cultured stem cells to rule out any microbial contamination [9].
