Stem Cells and Cell Therapy

Stem cells are divided into three different categories totipotent, pluripotent, and multipotent. A description of the genesis of stem cells is shown in Fig. 4.11. 

Totipotent stem cells are obtained from embryos that are less than 5 days old. These cells have the full potential to develop into another individual and every cell type. 

After about 5 days and several cycles of cell division, the totipotent cells form a hollow sphere of cells called a blastocyst. The blastocyst has an outer layer of cells surrounding clusters of cells. Those cells on the outside continue 

Stem cells removed and grown In Petri dish 

Cell differentiation (e.g., musice, nerve, Islet cells) 

---

Stem cells and cell therapy is the use of pluripotent and multipotent cells to generate healthy cells and tissues to replace the faulty ones in disease conditions. The main ethical questions are the source of the cells and the possibility of cloning humans. 

Weiss, D. J., Rolls, J. K., Ortiz, L. A., Panoskaltsis-Mortari, A., and Prockop, D. J. 2008. Stem cells and cell therapies in lung biology and lung diseases. Proc Am Ihorac Soc, 5,637-67. 

Additional future innovations likely to impact upon pharmaceutical biotechnology include the development of alternative product production systems, alternative methods of delivery and the development of engineered cell-based therapies, particularly stem cell therapy. As mentioned previously, protein-based biotechnology products produced to date are produced in either microbial... 

Involvement of several proteolytic enzymes, secretases, is probably crucial for this process but other hypotheses, including, for example, cholinergic transmission or accumulation of metal ions, have also been considered. Future perspectives in this area concern the search for novel pharmaceuticals that cross the blood-brain barrier, without side effects (e.g., the dyskinesias of L-Dopa), or potent and selective inhibitors of improper cleavage of amyloid protein, or even stem cell therapy to restore neuronal cells. 

Stem cell therapy— both somatic cell and germ cell... 

Stem Ceii Therapy With stem cell therapy, the aim is to grow body parts to replace defective human organs and nerves. The stem cells are harvested from... 

Stem cell therapy involves infusion of specialized cells utilized to perform specific functions. The traditional use of cell therapy includes harvest and cryopreservation of autologous hematopoietic cells either from the bone marrow (old approach) or mobilization and pheresis of hematopoietic stem cells from peripheral blood using stem cell-mobilizing cytokines such as hematopoietic colony-stimulating factors (G-CSF, GM-CSF) or chemokine inhibitors (AMD-3100). A more recent stem cell source is umbilical cord blood that has rich pleuripotent potential and can engraft at lower doses than bone marrow or mobilized peripheral blood stem cells. 

However, new insights into the mechanisms of cardiac repair have provided evidence that the adult heart can at least partially repair injury and that vasculogenesis may not occur solely during embryonic development. These insights, in turn, have sparked strong interest in the field of stem cell therapy [2, 3]. Prompted by evidence that adult bone marrow harbors a reservoir of plastic cells [4], animal experiments have generated evidence... 

The field of stem cell therapy has benefited from the work of numerous basic and clinical scientists whose studies have greatly improved our understanding of the processes involved in cardiac repair and neovascularization. The creation of new blood vessels (neovascularization) requires the formation of new mature endothelial cells. In this process, the new... 

Adult bone marrow-derived stem cells are presently the cell types most widely utilized in cardiac stem cell therapy. A heterogeneous subset, termed autologous bone marrow-derived mononuclear cells (ABMMNCs), is composed of small amounts of stromal or MSCs, HPCs, EPCs, and more committed cell lineages, such as natural killer lymphocytes, T lymphocytes, B lymphocytes, and others [2]. 

Endothelial progenitor cell numbers appear to decrease in the presence of risk factors for CAD and to correlate negatively with Framingham cardiovascular risk factors [31]. Therefore, stem cell therapy with EPCs may prove very useful in the clinical setting of cardiovascular disease. The kinetic and biological properties of EPCs may be especially appropriate for autologous transplantation. EPCs may also be safe to use in elderly and diabetic patients, populations in which they do not tend to migrate as much or induce neovascularization [68]. 

The transdifferentiation of HSCs into a mature hematopoietic fate (e.g., endothelium) in the heart is less controversial [148]. In animal models of stem cell therapy in ischemic heart disease, the evidence points toward increased neovascularization (with reduced myocardial ischemia) and consequent improvement in cardiac function [149-151]. Bone marrow stem cells may directly contribute to an increase in contractility or, more likely, may passively limit infarct expansion and remodeling. Unfortunately, the limitations of the present animal models leave this question unanswered. 

Thum et al. [153] have provided an alternative explanation for the functional improvement seen with stem cell therapy after AMI. They propose that stem cells produce an immunomodulating effect that would, in turn, reduce scar formation, repress cardiac apoptosis, and, thus, improve cardiac function (Fig. 7.14). 

Despite many unresolved issues related to treatment dose, timing, and delivery, the clinical potential of stem cell therapy for cardiovascular disease is enormous. The expectations of both patients and clinicians for this new therapeutic modality, however, are high and to achieve the full potential stem cell therapy has to offer will require continued cooperation and future close collaboration between basic and clinical scientists. 

With regard to left ventricular function, cardiac stem cell therapy is well tolerated overall. No proar-rhythmic effects have been observed to date with ABMMNC therapy, although other deleterious effects are possible. Early concerns about abnormal transdifferentiation and tumorigenesis have subsided, but the potential for accelerated atherogen-esis remains, given the limited clinical experience... 

Acronyms and Definitions Mesenchymal Stromal Cells Somatic Stem Cell Therapy Good Manufacturing Practice Cell-Based Medicinal Products Human Platelet Lysate... 

Stem cell therapy holds the promise to treat a broad range of diseases and injuries. The promise of stem cell therapy, particularly in the CNS, is in regenerating and reconstructing the original pathway to promote functional recovery, but it may be years before it emerges as... 

Reproduced with permission from The Thomson Corporation and Taupin P ADA-transduced hematopoietic stem cell therapy for ADA-SCID. IDrugs (2006) 9(6) 423-30. Copyright 2006, The Thomson Corporation. 

Hoffman, R.M. 2005. Gene and stem cell therapy of the hair follicle. Methods Mol Biol 289 437. 

Saha, M., and Ferro, A. 2006. Cardiac stem cell therapy present and future. Br. J. Clin. Pharmacol. 

Tumorigenicity studies are also needed for certain cell therapy products based on the specific product attributes and clinical indications. Somatic cell therapy includes cells from various sources such as adult cells derived from the individual being treated (autologous), cells donated from one human to another (allogeneic), and cells from an animal source and used for human treatment (xenogeneic). Stem cell therapy includes cells derived from a variety of adult... 

---