**4. Conclusion**

The indications for HSCT are continually changing and expanding rapidly beyond the traditional use as a treatment for malignant and nonmalignant diseases. The inclusion of cord blood as a source of stem cells and the availability of reduce intensity regimens has allowed us to expand the indications for HSCT to patients who otherwise would not meet accepted criteria for conventional HSCT. The field of HSCT is continually growing and a great deal of additional research is needed to continue to improve our outcomes. This is an exciting time in HSCT with many new avenues becoming available for patients.

### **5. References**


IPEX syndrome is a rare, fatal autoimmune disorder caused by mutations in the forkhead box protein 3 (FOXP3) genes leading to the disruption of signaling pathways involved in regulatory T-Lymphocyte function. Patients with IPEX syndrome often present in early infancy and without therapeutic intervention, affected male patients usually die within the first or second year of life. These patients require supportive therapy including parental nutrition, insulin, antibiotics and blood transfusions. Immunosuppressive therapy has been used with variable improvement in symptoms. Correction of the dysregulated immune system can be achieved by allogeneic HSCT using a suitable donor. Although, HSCT is the only viable option for long-term survival, patients are usually very ill to tolerate traditional myeloablative conditioning regimens. Recent studies reported the successful outcome of HSCT using a low-intensity, nonmyeloablative conditioning regimen in 2 patients with IPEX

**3.4.3 Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)** 

syndrome and significant pre transplant risk factors (Burroughs, 2010; Rao, 2007).

EB is a group of blistering skin disorders resulting from mutations in genes encoding protein components of the cutaneous basement membrane zone. HSCT has been shown to ameliorate the deficiency of the skin-specific structural protein in children with EB (Fujita,

The indications for HSCT are continually changing and expanding rapidly beyond the traditional use as a treatment for malignant and nonmalignant diseases. The inclusion of cord blood as a source of stem cells and the availability of reduce intensity regimens has allowed us to expand the indications for HSCT to patients who otherwise would not meet accepted criteria for conventional HSCT. The field of HSCT is continually growing and a great deal of additional research is needed to continue to improve our outcomes. This is an

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**3.4.4 Epidermolysis bullosa (EM)** 

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**17** 

*HemoGenix, Inc* 

*U.S.A.* 

**Hematopoietic Stem Cell Potency for Cellular** 

Potency is the quantitative measurement of biological activity of a product (European Medicines Agency (EMA), 2008). Potency provides assurance that production and manufacture demonstrate consistency and provides information on stability and performance of the product. It also allows correlation with the clinical response and can help avoid product failure or toxicity due to the improper dose of the product being administered. For biopharmaceutical products such as drugs, growth factors and cytokines, vaccines etc., measurement of potency to predict dose has been a routine procedure for many years. Cells, on the other hand, are complex living entities that are continuously in flux. The potency of cells can change depending on numerous physiological and external environmental factors. Yet, with the increased number of cellular therapeutic applications and clinical regimen involving numerous cell types, the need to reliably and reproducibly measure biological and functional activity to meet the requirements of potency and ensure patient safety is of increasing importance (EMA, 2008; U.S. Food and Drug Administration,

Determining the potency of a stem cell therapeutic can be a daunting task, especially if knowledge of the system biology, physiology and regulation is limited. In contrast, the hematopoietic system has proven to be not only an excellent model for stem cell biology, but also a model system for proliferation and differentiation in different applications. One of these applications is stem cell transplantation, a procedure that had its origins during the 1950s, became a quantitative assay in mice in 1961 (Till & McCulloch), and a routine clinical procedure in the 1970s (Santos et al. 1972; Thomas et al. 1977; Santos, 1983) Since that time, the number of human bone marrow transplantations reached a peak in the late 1990s (National Marrow Donor Program (NMDP); Pasquini & Wang, 2010) and has been declining to be replaced by alternative stem cell sources derived from mobilized peripheral blood (Haas et al. 1990; Koerbling et al. 1990; Sohn et.al. 2002) and umbilical cord blood

Regardless of the tissue source, a successful transplant of stem cells is dependent upon the ability of the transplanted stem cells to lodge or "seed" in the bone marrow and begin the process of proliferation to produce lineage-specific progenitor cells. These differentiate into functionally mature circulating neutrophils, platelets and erythroid cells, the number of

**1. Introduction** 

(FDA), 2011).

(Broxmeyer et al. 1989; Gluckman et al. 1989).

**Therapeutic Transplantation** 

Karen M. Hall, Holli Harper and Ivan N. Rich

