الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Hematopoietic stem cell transplantation (HSCT) is a medical procedure that aims at regaining the hematopoietic system function after administration of chemotherapy and this treatment modality is classified according to the source of the hematopoietic stem cells that infused to the patient in to:
1- Autologous hematopoietic stem cell transplantation in which the self-renewing progenitor cells are derived either from the patient’s own marrow or peripheral blood.
2- Allogeneic stem cell transplantation in which the progenitor cells are derived from a cell donor other than the patient.
Autologous hematopoietic stem cell transplantation is best described as one step in the treatment plan for malignant (usually hematological diseases) and is not considered as therapeutic entity in itself.
Autologous hematopoietic stem cell transplantation is used in the treatment of the following diseases: Multiple myeloma, Aggressive Non-Hodgkin lymphoma , Hodgkin disease , Acute myeloid leukemia , Neuroblastoma, Germ cell tumors , Autoimmune disorders such as (systemic lupus erythematosis [SLE], systemic sclerosis) and Amyloidosis.
Autologous hematopoietic stem cell transplantation process can be summarized in to the following steps: mobilization, collection, preparation of product for storage, cryopreservation, administration of preparative regimen, stem cell transplantation, engraftment and recovery.
HSCs reside within a specialized microenvironment that is located in the bone marrow, this microenvironment is called HSC niche which is divided in to two anatomical and functional niches: a vascular niche and an endosteal niche.
HSCs homing in the bone marrow niche is mediated through some adhesive and chemotactic interactions as Perivascular MSCs, sinusoidal endothelial cells, and osteoprogenitors express adhesion molecules such as :VCAM-1/CD106 that binds its receptor integrin α 4 β1expressed by HSCs, trans membrane SCF (kit ligand) that binds its receptor c-Kit (CD117) on HSCs, Stromal cell–derived factor-1 (SDF-1/CXCL12) secreted by niche cells and its receptor CXCR4 on HSCs,CD44 a cell surface molecule which interacts with osteopontin and hyaluronic acid.
The CD44 is a cell adhesion molecule that is encoded by one gene located on chromosome 11. CD44 is an integral membrane glycoprotein which shows high structural heterogeneity that results from a wide variety of protein polymorphisms and post-translational modifications.
CD44 standard (CD44s) is the most abundant isoform, expressed by most mammalian cells and involved in hyaluronan uptake and degradation, angiogenesis, wound healing, tissue formation and patterning. CD44s is also a critical signaling receptor.
In contrast, CD44 variants (CD44v) are up-regulated in neoplasia , involved in tumor metastasis and related to tumor aggression.
CD44 is the most common receptor for hyaluronan, and hyaluronan uptake and degradation occurs in a CD44-dependent manner. Hyaluronan is an important component of the hematopoietic stem cell (HSC) niche, participating in HSC anchorage in the endosteal region as well as functioning in HSC proliferation and differentiation.
The aim of the present study was to assess the impact of CD44 single nucleotide polymorphism on the efficacy of mobilization of CD34+ hematopoietic progenitor cells in patients scheduled for autologous transplantation.
To achieve this goal the study was conducted on 46 patients who were eligible for autologous HSC mobilization and transplantation. Patients were recruited from the stem cell transplantation unit in EL Mowasah hospital.
All patients in the study were subjected to the following: Full history taking,
- Complete clinical examination, Laboratory investigations.
- CD34 cell counting from the apheresis product was done by flow cytometry.
- Genotyping for CD44 gene SNPs rs (13347) was done by allelic discrimination using the 5` nuclease assay using Taqman real time PCR.
The present study didn’t find any statistical relation between the mobilization efficacy of HSCs and the age, sex and the type of the primary disease.
The present study results showed that there was a statistically significant difference between the CD44 SNP genotypes and the CD34 yield and the mobilization efficacy of the CD34 cells in to the peripheral blood, with the C allele related to good HSC mobilization response and the T allele related to poor mobilization response.