Stem Cell Therapy

In order to discover the ways for the remedy of diseases, studies in therapeutic approaches have been doing widely and kept increasing at accelerated pace. A lot of research areas had emerged for that purpose including one of the most fascinating and highly active areas at present, stem cells therapies. Due to self-renewal property and differentiation capability of stem cell, it becomes a new hope in modern treatment.
The first successful case of stem cell therapy in human was reported in 1959. Bone marrow restorations were observed in leukemia patients who received total body irradiation subsequent by intravenous injection of their twins’ bone marrow (Thomas et al, 1957). Nevertheless, that effect was transient and the following bone marrow transplantation attempts in non-twin patients and donors can eventually lead to patient’s death from graft-versus-host disease (Mathé et al, 1965). During that time, the safety of hematopoietic cells transplantation was not guaranteed because of the limited knowledge in human histocompatibility and immunosuppression. However, the turning point came after the discovery of human leucocyte antigen (HLA) groups (Dausset, 1958; van Rood et al, 1958), HLA typing and compatibility testing were performed prior to the transplantation. In addition, the improvement of immunosuppressive protocol also helps bringing the bone marrow transplantation to become more and more successful (Donnall and Hutchinson, 1999).
Although the success rate of hematopoietic stem cell therapy was great, patients’ mortality still happened as a result of some factors. Besides from graft-versus-host disease which have previously mentioned, infection contributes for most cases of patient death (Kernan et al, 1993). In allogeneic transplantation, patient’s immunity needs to be suppressed to avoid graft rejection. During such immunoincompetence period, there is a high risk that patient might get infected either from viral reactivation, hepatitis B (Hammond et al, 2009) and herpes simplex virus (Pillay et al, 1992) for instance, or other opportunistic infections such as Candida species (Wingard et al, 1991) and cytomegalovirus (Leung et al, 1999). However, this problem could be minimized in nonmalignant patients by using autologous transplantation.
Cell contamination is another risk factor in stem cell therapies that should be concerned. Since stem cells are human-derived products, contamination could occur at any steps in process. Start from stem cell sources or donors, they might carry viruses, parasites or diseases that can infect patients after transplantation. So, donor screening tests and assessment need to be performed (Sacchi et al, 2008). Medical and familial histories of donors are also essential and should be scrutinized in order to avoid getting stem cells from someone that might transmit congenital defect, autoimmunity or malignant disease to the patient (Niederwieser et al, 2004). Harvesting and culturing of stem cells are the processes that might have caused the microbial contamination as well, thus, sterile technique must be cautiously conducted during those steps.
Up till now, bone marrow or hematopoietic stem cells transplantation has been proofed to cure many diseases such as aplastic anemia, acute and chronic leukemia, and severe thalassemia with low complications in patients (Thomas et al, 1975; Lucarelli et al, 1984). As a result from the prosperous in hematopoietic stem cell transplantation, researchers and physicians are trying to extend this aspect to other diseases and different types of stem cell. Mesenchymal stem cell and embryonic stem cell are two of those that have been broadly used in studies of stem cell therapies. Immense potential in in vitro and animal treatments of stem cells were observed in many diseases including breast cancer (Li et al, 2010), muscular dystrophy (Sampaolesi et al, 2003), acute renal failure (Morigi et al, 2004) and diabetes mellitus type 1 (Kofman et al, 2004) as reported in previous literatures. When it comes to clinical trials in human, however, the controversial exist. Stem cell did not show impressive effects as they did in bone marrow transplantation or preclinical models. Furthermore, some cases that showed dangerous complication of stem cell therapy were reported recently. A teenage boy who repeatedly received fetal neural stem cell injection for ataxia telangiectasia therapy, four years later, had found to develop nonself-origin brain tumor derived from more than one donor transplanted stem cells (Amariglio et al, 2009). This case provides the first solid evidence to proof that transplanted stem cells could give rise to malignant transformation. Another interesting case was reported in lupus nephritis patient who undergone autologous hematopoietic stem cell transplantation by direct renal injection. Angiomyeloproliferative lesions which believed to be derived or induced by stem cells were developed at the injection sites, moreover, hemodialysis and hematuria were noticed. Patient’s symptoms gradually deteriorated and finally died of sepsis after 2 years have passed (Thirabanjasak et al, 2010). These cases raise even more questions in stem cell therapy.
Although there are some risk factors in using stem cell for therapeutic approaches, hematopoietic stem cell therapy by bone marrow transplantation has already been proofed to be safe if donors’ background and screening, cell contamination, HLA matching and opportunistic or nosocomial infections during immunocompromised period were carefully monitored and controlled. Still, other types of stem cell therapies, despite of their good therapeutic efficacy, are remain in experimental stage and need more data to support and demonstrate the safety in clinical trials. More understanding of stem cell biology is also required in order to keep stem cell under controlled and avoid some complications that they might cause. So, to pave the way for successful stem cell therapy, research in this extent is needed to pursue to maximized therapeutic efficiency with highest safety in patients.

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