Umbilical Cord Blood Transplant (UCBT) is a type of allogenic haematopoetic stem cell transplant. Stem cell transplantation as a mode of treatment of diseases was first successfully done by the pioneering work of a Nobel Prize Winner in Physiology or Medicine, E. Donnall Thomas in 1957. Throughout the past 50 years, numerous other researchers have improved the techniques of this previously highly risky procedure. Among the notable landmark in haematopoetic stem cell transplant include: advancement in immunogenetics of HLA, better immunosuppressive preparative regimen, improved control of infections, appearance of donor registries throughout the world and successful transplantation stories using haematopoetic stem cells from peripheral blood and the cord blood. These developments lead to a change in terminology from marrow transplantation to haematopoetic stem cell transplantation .
Inherited thalassaemia disease is commonly found in many countries of the world. Care of the disease requires comprehensive management strategies comprising of clinical management of both transfusion dependant thalassaemia (TDT) and non-transfusion dependant thalassaemia (NTDT). It also includes preventive measures such as screening programmes and genetic counseling in order to contain the genetic transmission. At the moment, the only cure is through haematopoeitic stem cell transplant (HSCT). This report illustrates thalassaemia disease prevalence in the Terengganu state and the evolution of care since National Thalassaemia Programme was launched in 2009.
Mesenchymal stem cells (MSCs) derived from human umbilical cord (UC) have been considered as an important tool for treating various malignancies, tissue repair and organ regeneration. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are better alternative to MSCs that derived from bone marrow (BM-MSCs) as they are regarded as medical waste with little ethical concern for research and easily culture-expanded. In this present study, the foetal distal end of human UC was utilised to generate MSC by explant method. Upon in vitro culture, adherent cells with fibroblastic morphology were generated with rapid growth kinetics. Under the respective inductive conditions, these cells were capable of differentiating into adipocytes and osteocytes; express an array of standard MSC's surface markers CD29, CD73, CD90, CD106 and MHC-class I. Further assessment of immunosuppression activity revealed that MSCs generated from UC had profoundly inhibited the proliferation of mitogen-activated T lymphocytes in a dosedependent manner. The current laboratory findings have reinforced the application of explant method to generate UCMSCs thus, exploring an ideal platform to fulfil the increasing demand of MSCs for research and potential clinical use.
Current clinical trials that evaluate human pluripotent stem cell (hPSC)-based therapies predominantly target treating macular degeneration of the eyes because the eye is an isolated tissue that is naturally weakly immunogenic. Here, we discuss current bioengineering approaches and biomaterial usage in combination with stem cell therapy for macular degeneration disease treatment. Retinal pigment epithelium (RPE) differentiated from hPSCs is typically used in most clinical trials for treating patients, whereas bone marrow mononuclear cells (BMNCs) or mesenchymal stem cells (MSCs) are intravitreally transplanted, undifferentiated, into patient eyes. We also discuss reported negative effects of stem cell therapy, such as patients becoming blind following transplantation of adipose-derived stem cells, which are increasingly used by 'stem-cell clinics'.
An outstanding amount of resources has been used in research on manipulation of human stem cells, especially mesenchymal stem cells (MSCs), for various clinical applications. However, human MSCs have not been fully utilized in clinical applications due to restrictions with regard to their certain biosafety and bioefficacy concerns, for example, genetic abnormality, tumor formation, induction of host immune response and failure of homing and engraftment. This review summarizes the biosafety and bioefficacy assessment of human MSCs in terms of genetic stability, tumorigenicity, immunogenicity, homing and engraftment. The strategies used to reduce the biosafety concerns and improve the bioefficacy of human MSCs are highlighted. In addition, the approaches that can be implemented to improve their biosafety and bioefficacy assessment are briefly discussed.
Mesenchymal stem cells (MSC) are multipotent, self-renewing cells that can be found mainly in the bone marrow, and other post-natal organs and tissues. The ease of isolation and expansion, together with the immunomodulatory properties and their capability to migrate to sites of inflammation and tumours make them a suitable candidate for therapeutic use in the clinical settings. We review here the cellular mechanisms underlying the emerging applications of MSC in various fields.
Multipotent mesenchymal stem cells (MSCs) have been employed in numerous pre-clinical and clinical settings for various diseases. MSCs have been used in treating degenerative disorders pertaining to the eye, for example, age-related macular degeneration, glaucoma, retinitis pigmentosa, diabetic retinopathy, and optic neuritis. Despite the known therapeutic role and mechanisms of MSCs, low cell precision towards the targeted area and cell survivability at tissue needing repair often resulted in a disparity in therapeutic outcomes. In this review, we will discuss the current and feasible strategy options to enhance treatment outcomes with MSC therapy. We will review the application of various types of biomaterials and advances in nanotechnology, which have been employed on MSCs to augment cellular function and differentiation for improving treatment of visual functions. In addition, several modes of gene delivery into MSCs and the types of associated therapeutic genes that are important for modulation of ocular tissue function and repair will be highlighted.
Mature T and natural killer (NK) cell non-Hodgkin lymphoma (T-NHL) has a poor prognosis. Data from existing retrospective and prospective studies have suggested that high-dose chemotherapy followed by autologous hematopoietic cell transplantation (auto-HCT) may improve the survival in patients with chemosensitive disease, either in the upfront or salvage setting. Auto-HCT is currently recommended to be used as frontline consolidation in peripheral T cell lymphoma not otherwise specified, angioimmunoblastic T cell lymphoma, anaplastic large cell lymphoma-anaplastic lymphoma kinase negative, NK/T cell (disseminated), and enteropathy-associated T cell lymphoma. However, about one-third of patients never reach transplantation because of early relapse or refractory disease. Allogeneic hematopoietic cell transplantation (allo-HCT), via its immunologic graft-versus-lymphoma effect, has been used to salvage patients with relapsed or refractory disease, resulting in long-term disease-free survival in a fraction of patients. However, the higher risk of transplant-related mortality due to regimen-related toxicities, graft-versus-host disease, and post-transplant infectious complications continues to limit the mainstream adoption of allo-HCT for this disease. Despite that, allo-HCT has been incorporated as part of the frontline treatment for aggressive subtypes of T-NHL, such as γδ T cell lymphoma and aggressive NK cell leukemia. Recent attempts to incorporate novel targeted T cell directed therapies into the treatment pathway of T-NHL may enhance treatment response and enable more patients to reach transplant, offering an alternative means of treating this disease.
The concept of regenerative endodontics wherein one can replace damaged pulp structures and recuperate the functionality in erstwhile necrotic and infected root canal systems has been a cutting-edge technology. Though the notion started as early as the 1960s, even before the discovery of stem cells and regenerative medicine, it was in the 2000s that this procedure gained momentum. Ever since then, researchers continue to discover its essential benefit to immature teeth and its ability to overcome the caveats of endodontic therapy, which is commonly known as root canal treatment. Further, through this therapy, one can redevelop root even in immature teeth with necrotic pulps, which overall helps in maintaining skeletal and dental development. Past literature indicates that regenerative endodontic procedures seem to be successful, especially when compared with other conventional techniques such as Mineral Trioxide Aggregate apexification. Besides, many clinicians have begun to apply regenerative endodontic procedures to mature teeth in adult patients, with several clinical case reports that have shown complete resolution of signs and symptoms of pulp necrosis. Generally, the three most desirable outcomes anticipated by clinicians from this procedure include resolution of clinical signs and symptoms, root maturation and redevelopment of the neurogenesis process. Despite this, whether these objectives and true regeneration of the pulp/dentin complex are achieved is still a question mark. Following the discovery that regenerative endodontics indeed is a stem cell-based treatment, addressing the fundamental issue surrounding stem cells might assist in achieving all identified clinical outcomes while favoring tissue formation that closely resembles the pulp-dentin complex.
Sarcopenia is a common condition in the geriatric population. It refers to age-related and progressive decline in muscle mass and function, which has a great impact on one's mobility and quality of life. Patients with sarcopenia are mainly treated with nutritional therapy, exercise therapy, or a combination of both. Since the identification of mesenchymal stem cells (MSCs) several decades ago, many studies have explored the application of MSCs in the field of regenerative medicine. MSCs are popular candidates for cell-based therapy owing to their multipotent nature and immunomodulatory properties. Even though MSCs do not naturally differentiate into myogenic cells, they are important players in skeletal muscle health, as MSCs support myogenic differentiation of other cells and promote recovery of injured skeletal muscle. Recent studies have found that MSCs may be of benefits in the treatment of sarcopenia. This article gives an overview of sarcopenia and the role of MSCs in skeletal muscle homeostasis. It also discusses the therapeutic potential of MSCs and their derivatives, as well as the underlying mechanisms of the therapeutic effects of MSCs and MSC-based products in sarcopenia.
The lack of curative therapies for neurodegenerative diseases has high economic impact and places huge burden on the society. The contribution of stem cells to cure neurodegenerative diseases has been unraveled and explored extensively over the past few years. Beyond substitution of the lost neurons, stem cells act as immunomodulators and neuroprotectors. A large number of preclinical and a small number of clinical studies have shown beneficial outcomes in this context. In this review, we have summarized the current concepts of stem cell therapy in neurodegenerative diseases and the recent advances in this field, particularly between 2010 and 2012. Further studies should be encouraged to resolve the clinical issues and vague translational findings for maximum optimization of the efficacy of stem cell therapy in neurodegenerative diseases.
Allogeneic BMT was performed in Indonesia, but had to be stopped prematurely because of the small number of patients. In the beginning, only patients with sufficient financial resources to travel to western countries could undergo transplant procedures. When neighbouring countries (Singapore and Malaysia) began performing transplant, patients were referred to those centres. In both countries, the procedure is more economical and therefore patients come from a broader range of economic classes. The Indonesian hematologist must deal with the post-transplantation side effects, such as GVHD, which are mostly of the chronic type of GVHD. The types of the post-transplant complications do not differ too much from other centres and need the same treatment used in the transplant centres. Hematologists in Indonesia also treat complications of HSCT performed in other countries. When there is no recovery of HSCT development in Indonesia so far, many commercially oriented companies or centres from other countries see Indonesia as a good commercial market and offer services, some of which are not scientifically sound. One of the main problems is umbilical cord blood stem cell banking from foreign countries, which is eagerly offered to parents expecting a baby. Moreover, parents are not fully protected by law. In conclusion, Indonesia needs to revive its own HSCT program to serve and protect its own patients of being used as commercial targets by other countries.
Stem cell transplantation is a generic term covering different techniques. However there is argument over the pros and cons of autologous and allogeneic transplants of mesenchymal stem cells (MSCs) for regenerative therapy. Given that the MSCs have already been proven to be safe in patients, we hypothesize that allogeneic transplantation could be more effective and cost-effective as compared to autologous transplantation specifically in older subjects who are the likely victims of degenerative diseases. This analysis is based on the scientific logic that allogeneic stem cells extracted in large numbers from young and healthy donors could be physiologically, metabolically and genetically more stable. Therefore stem cells from young donors may be expected to exhibit higher vigor in secreting trophic factors leading to activation of host tissue-specific stem cells and also be more efficient in remodeling the micro-environmental niche of damaged tissue.
Peripheral blood stem cells (PBSC) mobilised with growth factor with or without chemotherapeutic regimens, are used increasingly in both autologous and allogeneic transplantation. Previously, many PBSC harvests are used directly without ex vivo manipulation, and these PBSC have been shown to be contaminated with tumour cells, which may contribute to subsequent relapses post transplantation. Therefore, requirement for purging of malignant cells from the harvest has initiated the use of various methods to reduce tumour cell contamination of the graft by the positive selection of CD34+ progenitor cells or negative selection of tumour cells using other cell-specific antigens. We report here our local experience with the CliniMACS (magnetic-activated cell separation system) in eight adult patients with haematologic malignancies.
Autogenous bone graft is the gold standard for fusion procedure. However, pain at donor site and inconsistent outcome have left a surgeon to venture into some other technique for spinal fusion. The objective of this study was to determine whether osteogenesis induced bone marrow stem cells with the combination of ceramics granules (HA or TCP/HA), and fibrin could serve as an alternative to generate spinal fusion. The sheep's bone marrow mesenchymal stem cells (BMSCs) were aspirated form iliac crest and cultured for several passages until confluence. BMSCs were trypsinized and seeded on hydroxyapatite scaffold (HA) and tricalcium phosphate/hydroxyapatite (TCP/HA) for further osteogenic differentiation in the osteogenic medium one week before implantation. Six adult sheep underwent three-level, bilateral, posterolateral intertransverse process fusions at L1-L6. Three fusion sites in each animal were assigned to three treatments: (a) HA constructs group/L1-L2, (b) TCP/HA constructs group/L2-L3, and (c) autogenous bone graft group/L5-L6. The spinal fusion segments were evaluated using radiography, manual palpation, histological analysis and scanning electron microscopy (SEM) 12 weeks post implantation. The TCP/HA constructs achieved superior lumbar intertransverse fusion compared to HA construct but autogenous bone graft still produced the best fusion among all.
No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy.
Adult ocular stem cells have the potential to restore vision in patients previously deemed incurable. This review summarizes strides in stem cell research and stumbling blocks that must be overcome to enable treatment viability in ophthalmology.
Spinal cord injuries (SCIs) are a common form of trauma that leaves a huge trail of morbidity and human suffering in its wake. They occur mostly among the young, causing severe physical, psychological, social and economic burdens. The treatment of this condition has rather been disappointing; most of the management strategies being mainly supportive and prophylactic. In recent years there has been an emerging interest in the use of stem cells to regenerate the nervous tissue that has been damaged or lost. Although there has been much hype and unfounded hope, modest successes have been witnessed, and it is possible that these therapeutic strategies may have much more to offer in the future. This paper will review the current strategies of exploring cell-based therapies, mainly different types of stem cells to treat SCI along with the evidence that has been accumulated over the past decade in a rational bench-to-bedside approach. Furthermore, critical aspects such as the mode of delivery and ethical considerations are also discussed along with feasible suggestions for future translational research to provide a contextual picture of the current state of advancements in this field. The impediments to regeneration in the site of injury are briefly explained along with the benefits and drawbacks of different cell types used in the treatment of this condition. We hope that this review will offer a significant insight into this challenging clinical condition.
Following hematopoietic stem cell transplantation (HSCT), it is important to determine whether engraftment is successful and to track the dynamic changes of the graft. Tandem repeats such as minisatellites and microsatellites are currently the most established markers for chimerism application. We have developed a reliable method to quantitatively evaluate engraftment status in post-allogeneic HSCT patients using variable number of tandem repeat (VNTR) markers and "lab-on-a-chip" microfluidic electrophoresis technology. Following identification of an informative marker by conventional polymerase chain reaction (PCR), donor chimerism percentage was calculated based on a standard curve generated from artificially mixed patient-donor DNA-specific alleles in serial dilutions. All PCR products were mixed with commercial gel dye and loaded into Agilent DNA 1000 microfluidic LabChips for DNA sizing and quantitation. In 44 patients, separation of pretransplant and donor DNA fragments was resolved clearly and accomplished rapidly within 30min. Chimerism analysis using this platform is able to detect an amount as low as 6.3% donor DNA with acceptable coefficient of variation values. We also demonstrated concordant chimerism analysis findings using both microchip tandem repeats and real-time PCR quantitation of insertion-deletion polymorphisms. This microchip platform obviates the need for fluorescently labeled primers or any post-PCR sample manipulation. Quantitative monitoring of post-HSCT chimerism status using microfluidic electrophoresis is a useful tool for both large- and small-scale post-HSCT chimerism centers.
Allogeneic stem cell transplantation is a treatment option for malignant and non-malignant disorders in children. For children with no HLA-matched sibling or related stem cell donors, there is the option of unrelated cord blood donors. At the University of Malaya Medical Centre (UMMC) in Kuala Lumpur, the first unrelated cord blood transplantation (CBT) was performed in October 1997. All unrelated CBT performed in UMMC relied on cord blood units imported from overseas. DNA typing with variable number of tandem repeat (VNTR) loci was done to qualitatively evaluate engraftment in 15 unrelated CBT. In all the fifteen cases that were evaluated, molecular evidence of engraftment or non-engraftment correlated with the clinical findings.