Mesenchymal stem cells (MSCs) are emerging as an attractive option for osteoarthritis (OA) of the knee joint, due to their marked disease-modifying ability and chondrogenic potential. MSCs can be isolated from various organ tissues, such as bone marrow, adipose tissue, synovium, umbilical cord blood, and articular cartilage with similar phenotypic characteristics but different proliferation and differentiation potentials. They can be differentiated into a variety of connective tissues such as bone, adipose tissue, cartilage, intervertebral discs, ligaments, and muscles. Although several studies have reported on the clinical efficacy of MSCs in knee OA, the results lack consistency. Furthermore, there is no consensus regarding the proper cell dosage and application method to achieve the optimal effect of stem cells. Therefore, the purpose of this study is to review the characteristics of various type of stem cells in knee OA, especially MSCs. Moreover, we summarize the clinical issues faced during the application of MSCs.
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The dose of CD34+ cells is known to influence the outcome of allogeneic peripheral blood stem cell (PBSC) and/or T-cell-depleted transplantation. A previous study proposed that 2×106 CD34+ cells/kg is the ideal minimum dose for allogeneic transplantation, although lower doses did not preclude successful therapy. In the case we present here, CD34+ cells were collected from a matched sibling donor on the day of allogeneic hematopoietic stem cell transplantation; however, the number of cells was not sufficient for transplantation. Consequently, PBSCs were collected three additional times and were infused along with cord blood cells from the donor that were cryopreserved at birth. The cumulative dose of total nuclear cells and CD34+ cells was 15.9×108 cells/kg and 0.95×106 cells/kg, respectively. White blood cells from this patient were engrafted on day 12. In summary, we report successful engraftment after infusion of multiple low doses of CD34+ cells in a patient with severe aplastic anemia.
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Over several decades, a hierarchical cancer stem cell (CSC) model has been established in development of solid cancers, including hepatocellular carcinoma(HCC). In terms of this concept, HCCs originate from liver CSCs. Clinically HCCs show a wide range of manifestations from slow growth to very aggressive metastasis. One of the reasons may be that liver CSCs originate from different cells. This review describes the basic concept of CSCs and the cellular origin of liver CSCs.
Primary liver carcinomas have been classified into hepatocellular carcinoma, cholangiocarcinoma, and combined hepatocellular-cholangiocarcinoma (CHC). CHC is a tumor containing unequivocal, intimately mixed elements of both hepatocellular carcinoma and cholangiocarcinoma. It forms a small but significant proportion of primary liver carcinomas. The origin and pathogenesis of CHC have not been well established. According to the 2010 WHO classification, CHCs are categorized into 2 groups: the classical type and a subtype with stem cell features. This review describes recent progress in pathology and classification of CHC.
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Hemorrhagic cystitis (HC) is a common complication after allogeneic transplantation. Early posttransplant HC occurs in association with cyclophosphamide, while later on HC results from viral infections such as polyomavirus BK (BKV) and adenovirus. We report here the case of a 57-year-old woman who received an instillation of cidofovir into the bladder for the treatment of hemorrhagic cystitis after allogeneic peripheral stem cell transplantation for her acute myeloid leukemia. Cyclophosphamide and busulfan were used as conditioning treatments. Cyclosporin was administered daily. On the 71st day after transplantation, the patient developed acute severe hemorrhagic cystitis, and BK virus was demonstrated in the urine samples using polymerase chain reaction. Her urinary symptoms did not improve in spite of palliative treatment, but a response was evident after intravesical cidofovir treatment.
Human bone marrow-derived mesenchymal stem cells (MSCs) are a rare population of undifferentiated cells that have the capacity of self renewal and the ability to differentiate into mesodermal phenotypes, including osteocytes, chondrocytes, and adipocytes in vitro. Recently, MSCs have been shown to reside within the connective tissue of most organs, and their surface phenotype has been well analyzed. Many reports showed that transplanted MSCs enhanced regeneration as well as functional improvement of damaged organs and tissues. The wide differentiation plasticity of MSCs was expected to contribute to their demonstrated efficacy in a wide variety of experimental animal models and in human clinical trials. However, new findings suggest that the ability of MSCs to alter the tissue microenvironment via secretion of soluble factors may contribute more significantly than their capacity for differentiation in tissue repair. This review describes what is known about the cellular characteristics and differentiation potential of MSCs, which represent a promising stem cell population for further applications in regenerative medicine.
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Myeloma is a disease of neoplastic B lymphocytes that synthesize abnormal amounts of immunoglobulin (Ig) or Ig fragments. Ten to twenty percent of myeloma patients are known to develop clinical evidence of amyloid-light chain(AL) amyloidosis. A high index of suspicion, however, is needed to make a diagnosis of amyloidosis. We report a case of multiple myeloma with AL amyloidosis successfully treated with autologous stem cell transplantation. In our case, the patient presented with longstanding abdominal discomfort and anterior chest pain. Chest X-ray showed several osteolytic changes on ribs. Endoscopic biopsy revealed massive amyloid deposits in the wall of stomach and rectum. Serum/urine protein electroporesis and bone marrow biopsy confirmed the diagnosis of multiple myeloma. At 18 months after high dose chemotherapy and autologous stem cell transplantation(ASCT), the patient maintained a complete response. In patients with multiple myeloma with AL amyloidosis, high dose chemotherapy and ASCT can be effective treatment strategy.
Bactground:The etiologies of treatment related mortality (TRM) after hematopoietic stem cell transplantation (HSCT) have been variable according to the disease status or the centers. We evlauated the etiologies of TRM for the pediatric patients at Yeungnam University Hospital (YNUH).
Materials and Methods:The records of 66 patients, 19 years of age or younger, who had HSCT at YNUH from September 1995 to August 2007 were reviewed.
Results :Among 66 patients, allogeneic bone marrow transplantation (Allo-BMT) was done in 21 (19 related, 2 unrelated), allogeneic peripheral blood stem cell transplantation (Allo- PBSCT) in 1, cord blood transplantation (CBT) in 12 (1 related, 11 unrelated), autologous peripheral blood stem cell transplantation (Auto-PBSCT) in 32 patients. The TRM rates of Allo-BMT, CBT, and Auto-PBSCT were 19%, 33.3%, and 12.5%, respectively. Among four patients who had TRM after Allo-BMT, two were related transplantation and the others were unrelated. All four patients developed severe acute GVHD of at least grade Ⅲ. Sepsis developed in three patients, acute renal failure (ARF) in two, veno-occlusive disease (VOD) and thrombotic microangiopathy (TMA) in one patient each. All four patients who had TRM after CBT had two mismatches in HLA-A, B, DR, and engraftment syndrome developed in three. Sepsis developed in all four patients, VOD in two, encephalopathy in two, TMA and ARF in one patient each. All four patients who had TRM after Auto-PBSCT developed sepsis and ARF in two, VOD and TMA in one patient each.
Conclusion :Although the number of cases were not large enough for firm conclusion, sepsis was the most common TRM after HSCT. Therefore, prevention and control of sepsis are very important in reducing TRM after HSCT. Outcomes of severe acute GVHD after Allo-BMT and engraftment syndrome after CBT are very poor and contribute for TRM. Continuous effort to reduce the incidence of GVHD and engraftment syndrome are needed.
Allogenic hematopoietic stem cell transplantation is one of the effective therapy for several hematologic malignancies. Transplantation preparative regimen is designed to eradicate the patient's underlying disease and immunosuppress the patient adequately to prevent rejection of donor's hematopoietic stem cells. so, Conventional myeloablative preparative regimens with high-dose chemotherapy or radiotherapy are related to high rate of morbidity and mortality. however, It has become clear that the high-dose therapy dose not eradicate the malignancy in some patients, and that the therapeutic benefit of allogenic transplantation is largely related to graft-versus-leukemia/graft-versus-tumor (GVL/GVT) effect. An new approach is to utilize less toxic, nonmyeloablative preparative regimens to achieve engraftment and allow GVL/GVT effects to developed. This strategy reduces the risk of treatment-related mortality and allows transplantation for elderly and those with comorbidities that preclude high-dose chemoradiotherapy.