Effectiveness of Stem Cell Treatments - Research Paper Example

Are Stem Cell Treatments Effective? Stem cells have an important function to perform in the physiology of life. They possess the remarkable ability to develop into different cell types in the early growth phase or the embryonic stage (Pera et al., 2000). Adult stem cells or somatic stem cells, on the other hand, function as an internal repair system lifelong in some organs such as the gut and bone marrow, to replenish damaged cells (Pessina and Gribaldo, 2006). The stem cells (SCs) being unspecialized cells, they can be stimulated into becoming specialized cells having specific functions under appropriate physiologic and laboratory conditions. SCs have the capacity to undergo cell division even after remaining quiescent for long periods of time yet, in organs such as the pancreas and the heart, they divide only in exceptional circumstances. The embryonic SCs (ESCs) are “pluripotent” cells which can produce tissues of all embryonic germ layers namely, endoderm, mesoderm and ectoderm. The adult SCs (ASCs) are “multipotent” cells having the capacity to generate a limited subset of cells (Lodi et al., 2011). of The characteristic ability of the stem cells to renew themselves continuously for long periods and differentiate into specific cell types under appropriate conditions (Zhong, 2008) make them good candidates for cell-based therapies in regenerative or reparative medicine, especially to treat conditions such as diabetes, heart disease, rheumatoid arthritis and several neurodegenerative diseases. Research on and application of ESCs for clinical use is a raging controversy. No regular human ESC therapies are available yet. According to the latest literature on the topic, the only on-going clinical trials employing ESC are being conducted on patients with spinal cord injury (Aznar and Sánchez, 2011). However, numerous trials have been/are being conducted with ASCs. Furthermore, therapies using ASCs have been available for years, e.g., bone marrow transplants. This article discusses some of the important clinical studies conducted with stem cells, specifically ASCs, and the results obtained pertaining to the efficacy and safety of such therapies. Clinical studies of stem cell therapy in: 1. Heart disease Myocardial infarction (MI) or the ischemic necrosis of the cardiac tissue occurs due to cardiovascular disease, leading to heart attack and causing damage to the cardiac tissue. The human heart muscle damaged by a heart attack does not heal naturally. The primary treatment protocol involves a rapid reperfusion of the infarct related coronary artery in order to curtail the ischemic area and reduce tissue damage (Lodi et al., 2011). Also, angioplasty is required to be conducted soon after, to effectively reestablish the coronary flow. A new strategy of restoring damaged heart tissue is through facilitating repair or regeneration of the tissue. Using ASCs as well as ESCs for heart muscle repair is, currently, an active area of research (stemcells.nih.gov). Autologous skeletal myoblast transplantation undertaken as a major multicenter study for MI treatment did not show any improvement especially with regard to the echocardiographic heart function (Menasche et al., 2008) but improvement in the ejection fraction (EF) was noted (Hagege et al., 2006). Adult human stem cells therapy (AHSCT) could successfully improve EF without causing adverse left ventricular remodeling (Schachinger et al., 2009). Also, in a multicenter double-blind study, intracoronary infusion of HSCs into the infarct artery of 204 patients with acute MI following successful reperfusion therapy was found to significantly reduce MI recurrence restenosis or arrhythmia which are two major adverse post-MI cardiovascular events (Schachinger et al., 2006). Bone marrow-derived mononuclear cells introduced with a catheter into the heart of 21 patients with severe heart failure in a nonrandomized, open-label study appreciably improved myocardial blood flow with associated enhancement of regional and global left ventricular function (Perin et al., 2003). 2. Diabetes Mellitus Type I diabetes mellitus (DM) is an auto-immune disorder (Trivedi et al., 2008). Cell-mediated autoimmune attack against insulin-secreting pancreatic β-cells is a regular occurrence in DM, necessitating life-long insulin replacement therapy, IRT (Vanikar et al., 2010). As a result of the reduction in the secretion of the hormone insulin that regulates glucose homeostasis, glucose accumulation in blood occurs in DM. Treatment of DM consists of the chronic introduction of exogenous insulin to re-establish glucose homeostasis. SC therapy can help regenerate pancreatic β-islet cells and thereby re-establish the normal secretion of human insulin (Lodi et al., 2011). Voltarelli et al. (2007) observed in a study conducted on 15 patients with type 1 DM without ketoacidosis, and injected intravenously with autologous nonmyeloablative hematopoietic stem cells while under high-dose immunosuppression, beta cell function improved in 13 out of 15 patients. AHSCT has also been found to lead to persistent insulin independence in most of the patients (Voltarelli et al., 2007; Couri et al., 2009). When accompanied by the administration of cyclophosphamide (CY) as well, insulin independence likely occurs as a result of synergistic action (Lodi et al., 2011). A study conducted with 5 insulinopenic DM patients with 0.6 to 10 years disease duration who were given intraportal xenogeneic-free allotropic human adipose tissue derived, insulin-making mesenchymal SCs (h-AD-MSC) showed an appreciable decrease in insulin requirements of up to 50%, and up to 26-fold increase in serum c-peptide levels (Trivedi et al., 2008). Vanikar et al. (2010) have reported successful cotransplantation of h-AD-MSC and cultured bone marrow (CBM) as IRT in a prospective open-labeled clinical trial consisting of 11 patients with 1- to 24-year disease duration. 3. Neurological disorders 3.1 Parkinson’s disease Parkinsons disease (PD) is an irreversible neurodegenerative disorder caused by selective and gradual loss of nigrostriatal dopamine-containing neurons. The degeneration of the dopamine-containing nerve cells leads to neural circuit anomaly in the basal ganglia that regulate movement, producing tremor, postural instability etc in the patients. Drugs such as levodopa/carbidopa, dopamine agonists, MAO-B inhibitors, and COMT inhibitors, can effectively control PD symptoms but not neural degeneration. SC therapy has been shown to stimulate the recovery of neuromotor function. Five parkinsonian patients who received first implants of human embryonic mesencephalic tissue unilaterally in the striatum and a second graft of the tissue into the putamen or the putamen plus the caudate nucleus exhibited significant movement improvements and increase in DOPA (dopamine precursor) levels (Lodi et al., 2011). 3.2 Spinal cord injury Spinal trauma can result in movement inability due to damage or destruction of neurons and glial cells, sensorial loss as well as lack of autonomic control. No treatment exists for spinal trauma. Olfactory mucosa is an important and readily available source of progenitor cells for neural repair. Intraspinal olfactory mucosal transplant in patients with spinal cord injury have shown encouraging results (Lodi et al., 2011). An improvement over 3 segments in light touch and pin prick sensitivity bilaterally, anteriorly and posteriorly was observed in 1out of the 6 patients who participated in a clinical trial of autologous transplantation of olfactory ensheathing cells into the spinal cord (Mackay-Sim et al., 2008). A phase I/II open-label and nonrandomized study conducted on 35 complete spinal cord injury patients involving autologous human bone marrow cell (BMC) transplantation by injection into the surrounding area of the spinal cord injury site, and the simultaneous administration of granulocyte macrophage-colony stimulating factor (GM-CSF) showed the treatment to cause no new deficit in patients. Significant neurological improvement was noted in the acute and subacute treated patients but not in the chronic treatment group (Yoon et al., 2007). 3.3 Amyotrophic lateral sclerosis A progressive death of central and peripheral motor neurons results in amyotrophic lateral sclerosis (ASL). The disease is characterized by progressive muscular paralysis due to degeneration of motor neurones in the primary motor cortex, corticospinal tracts, brainstem and spinal cord (Wijesekera and Leigh, 2009). The mutation of the superoxide dismutase enzyme gene is a likely cause of the disease. Currently, no pharmacologic treatment is available to restore the neural cells (Lodi et al., 2011). The treatment strategy, used for ALS, is to protect neurons from degeneration and to stimulate cell regeneration. Ex vivo expanded mesenchymal stem cells, suspended in autologous cerebrospinal fluid and transplanted into the spinal cord of patients with severe impairment of the lower limb from ALS were seen to cause a deceleration of the leg muscular strength loss and respiratory function decline (Lodi et al., 2011). The progression of the disease was delayed and the quality of life improved in ALS patients who were administered AHSCT suspended in autologous cerebrospinal fluid into the frontal motor cortex (Lodi et al., 2011). 4. Ocular surface diseases Visual loss is generally the outcome of ocular surface diseases that are characterized by persistent epithelial defects, corneal perfusion problems, chronic inflammation (Lodi et al., 2011). An important cause of ocular surface diseases is the limbal SC deficiency (LSCD). Restoration of the ocular environment is only possible through SC transplantation therapy. Stem cells, obtained from the limbus of the contralateral eye, and cultivated onto a fibrin substrate were grafted onto damaged corneas of 18 patients with limbal cell deficiency. The results of the multicenter study showed the occurrence of re-epithelialization, regression of inflammation and vascularization, and considerable improvement in visual acuity in 14 of the 18 patients (Rama et al., 2001). Acquired and hereditary LSCD can be corrected by limbal allograft. 5. Liver diseases Cirrhosis is a progressive and irreversible liver function loss produced by replacement of normal parenchymal tissue by scar tissue. Treatments generally attempt to prevent its progression and complications (Lodi et al., 2011). Liver transplant is the only treatment option for a terminally-ill case. In 9 patients with severe and biopsy-proven alcoholic liver cirrhosis AHSC expanded in vitro and injected into the hepatic artery, improvement in liver function parameters such as transaminase activity, bilirubin decrease and albumin increase were noted. A significant enhancement of proliferation indices such as alpha fetoprotein and proliferating cell nuclear antigen (PCNA) indicated that HSCs can promote as well as accelerate hepatic regeneration (am Esch et al., 2005). 6. Crohn’s disease Crohn’s disease is an inflammatory bowel disease. It is caused by the abnormal reaction of the body’s immune system which leads to an accumulation of the white blood cells in the lining of the intestines, producing chronic inflammation, and leading to ulcerations and bowel injury. Treatment of Crohn’s disease includes drugs such as anti-inflammatory drus, steroids and immunosuppressors, nutrition supplements, surgery, or a combination of these options. Autologous haematopoietic stem cell transplantation (HSCT) with unselected PBSC was found to be safe and could induce and maintain clinical remission in refractory Crohns disease patients (Cassinotti et al., 2008). When AHSCT was used in combination with high doses of the immunosuppressant cyclophosphamide, the clinical remission occurred with a disappearance of the disease symptom diarrhea, and a reduction in the abdominal pain (Burt et al., 2003). 7. Rheumatoid arthritis Rheumatoid arthritis (RA) is an autoimmune disease that leads to chronic inflammation of the joints. The disease is typically progressive and can cause destruction of the joints and functional disability. There is no treatment to cure rheumatoid arthritis. The general treatment strategy involves medication to reduce joint inflammation and pain, maximize joint function through exercise, and prevent joint destruction and deformity. The remission rate is quite poor (Lodi et al., 2011). A multicenter study involving 73 patients, with significant functional impairment due to RA which was resistant to conventional therapies, were administered autologous HSCT. The therapy did not cure, but recurrent or persistent disease activity could be subsequently controlled, sometimes in combination with antirheumatic drugs (Snowden et al., 2004). Fraudulent stem cell clinics Stem cell research is one branch of science that has generated incredible public interest. Stem cell therapies promise novel, sure fire treatment for several diseases for which conventional medicine is ineffective. Stem cell research is yet to mature fully before it can offer scientifically-proven treatment protocols. More painstaking research and carefully planned clinical trials are required to be conducted. But several privately-operated clinics around the world are already offering putative therapies to the public via the internet. One question that is yet to be answered unequivocally is whether stem cell therapies might cause cancer. It is, therefore, essential that people should be wary of the claims made by stem cell clinics online which only provide scientifically-inadequate and dubious data to promote their therapies. Conclusion Stem cell therapies hold much promise for the treatment of several disorders, including diabetes, neurodegenerative diseases, heart disease, autoimmune diseases and cancer. Numerous trials conducted with adult stem cells have shown ASCs to be as good as ESCs but without the controversy surrounding the use of ESCs. People should beware of dubious, privately-run clinics around the world that make scientifically-unproven claims about the efficacy of the stem cell therapies offered by them. References am Esch JS, Knoefel WT, Klein M, et al., 2005. Portal application of autologous CD133+ bone marrow cells to the liver: a novel concept to support hepatic regeneration. Stem Cells, 23(4):463-470. Aznar J & Sánchez JL, 2011. Embryonic stem cells: are useful in clinic treatments? 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