This article provides a brief review of the pathophysiology of osteoarthritis and the ontogeny of chondrocytes and details how physical exercise improves the health of osteoarthritic joints and enhances the potential of autologous chondrocyte implants, matrix-induced autologous chondrocyte implants, and mesenchymal stem cell implants for the successful treatment of damaged articular cartilage and subchondral bone. In response to exercise, articular chondrocytes increase their production of glycosaminoglycans, bone morphogenic proteins, and anti-inflammatory cytokines and decrease their production of proinflammatory cytokines and matrix-degrading metalloproteinases. These changes are associated with improvements in cartilage organization and reductions in cartilage degeneration. Studies in humans indicate that exercise enhances joint recruitment of bone marrow-derived mesenchymal stem cells and upregulates their expression of osteogenic and chondrogenic genes, osteogenic microRNAs, and osteogenic growth factors. Rodent experiments demonstrate that exercise enhances the osteogenic potential of bone marrow-derived mesenchymal stem cells while diminishing their adipogenic potential, and that exercise done after stem cell implantation may benefit stem cell transplant viability. Physical exercise also exerts a beneficial effect on the skeletal system by decreasing immune cell production of osteoclastogenic cytokines interleukin-1β, tumor necrosis factor-α, and interferon-γ, while increasing their production of antiosteoclastogenic cytokines interleukin-10 and transforming growth factor-β. In conclusion, physical exercise done both by bone marrow-derived mesenchymal stem cell donors and recipients and by autologous chondrocyte donor recipients may improve the outcome of osteochondral regeneration therapy and improve skeletal health by downregulating osteoclastogenic cytokine production and upregulating antiosteoclastogenic cytokine production by circulating immune cells.

Granulocyte colony-stimulating factor (GCSF) is currently the most widely used cytokine for stem cell mobilization. There are few studies suggesting GCSF administration may induce activation of both coagulation and endothelial cells that could favor the developing of thrombotic events. We report a 58-year-old female with vasculitis and renal impairment. She was found to have an underlying monoclonal gammopathy of unknown significance (MGUS). The monoclonal protein was felt to play a role in her underlying renal disease and peripheral neuropathy. She was considered a candidate for peripheral blood stem cell transplantation to manage the monoclonal protein. During stem cell mobilization with GCSF, she developed worsening of anemia; thrombocytopenia and worsening of renal function. She was diagnosed with thrombotic microangiopathy (TMA) which was successfully treated with therapeutic plasma exchange and rituximab. It is possible that GCSF may have directly (activating endothelial cells) or indirectly (activation of underlying autoimmune disorder) contributed to TMA in this patient.

Transplantation of adult human hepatic stem/progenitor cells (hHSPCs) has been considered as an alternative therapy, replacing donor liver transplantation to treat liver cirrhosis. This study assessed the antifibrotic effects of hHSPCs in mice with fibrosis induced by carbon tetrachloride (CCl4) and examined the actions of hHSPCs on the fibrogenic activity of human hepatic stellate cells (HSCs) in a coculture system. Isolated hHSPCs expressed stem/progenitor cell phenotypic markers. Mice were given CCl4 (twice weekly for 7 weeks) and hHSPC transplantation weekly. CCl4 induced advanced fibrosis (bridging fibrosis and cirrhosis) in mice, which was prevented by hHSPC transplantation. The liver of hHSPC-transplanted mice showed only occasional short septa and focal parenchymal fibrosis, and a 50% reduction in hepatic collagen, assessed by Sirius red stain histomorphometry. Moreover, the proteins for α-smooth muscle actin (α-SMA) and collagen I were decreased. While α-SMA, collagen α1(I), and tissue inhibitor of metalloproproteinase-1 mRNAs were decreased, matrix metalloproteinase (MMP)-1 mRNA was increased, consistent with decreased fibrogenesis. MMP-2 and transforming growth factor-Β were not affected. Alanine aminotransferase and aspartate aminotransferase were lower, suggesting improvement of liver function/damage. In coculture, hHSPCs elicited changes of α-SMA and fibrogenic molecules in HSCs similar to those observed in vivo, providing evidence for a functional link between hHSPCs and HSCs. A decreased HSC proliferation was noted. Thus, transplantation of hHSPCs prevents histogenesis of advanced liver fibrosis caused by CCl4. hHSPCs mediate downregulation of HSC activation coincident with modulation of fibrogenic molecule expression, leading to suppression of fibrogenesis both in vivo and in vitro.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18857号 / 医博第3968号 / 新制||医||1008(附属図書館) / 31808 / 京都大学大学院医学研究科医学専攻 / (主査)教授 前川 平, 教授 江藤 浩之, 教授 河本 宏 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20074号 / 医博第4167号 / 新制||医||1018(附属図書館) / 33190 / 京都大学大学院医学研究科医学専攻 / (主査)教授 木村 剛, 教授 羽賀 博典, 教授 瀬原 淳子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20618号 / 医博第4267号 / 新制||医||1023(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 髙折 晃史, 教授 羽賀 博典, 教授 江藤 浩之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21455号 / 医博第4422号 / 新制||医||1033(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 山下 潤, 教授 湊谷 謙司, 教授 浅野 雅秀 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Introduktion: Patienter med hematologisk cancer kan genomgå en stamcellstransplantation som behandling för att få nya blodbildande stamceller. Målet med transplantationen samt cytostatikabehandling är överlevnad för patienten och att bota malignitet.  Syfte: Att studera patienter med hematologisk cancer och deras upplevelser av att genomgå stamcellstransplantation.  Metod: En deskriptiv litteraturöversikt där 11 kvalitativa studier har granskats. Litteratursökningen gjordes via databaserna CINAHL och PubMed. Kvalitetsanalysen genomfördes med hjälp av SBU:s kvalitetsgranskningsmall. Resultatanalysen genomfördes enligt Fribergs femstegsmodell.  Resultat: Många negativa aspekter framkom men även positiva upplevelser inom några underkategorier. Många av deltagarna upplevde biverkningarna som begränsande, däribland fatigue som även kunde påverka dem en tid efter behandlingens slut. Flertalet kände sig rädda för att dö och återinsjukna i sjukdomen. Stöd från anhöriga, vårdpersonal och patienter var viktigt för att orka ta sig igenom behandlingsperioden. Skyddsisoleringen upplevdes av de flesta som jobbig, men kunde även kännas som en säker miljö för vissa. En övervägande andel av deltagarna var i behov av mycket information såväl inför som under stamcellstransplantationen. Slutsats: Personer som genomgår en stamcellstransplantation på grund av hematologisk cancer kan påverkas på många olika sätt, mestadels negativt där rädsla var förekommande. Biverkningar påverkade även återgången till vardagen. Skyddsisoleringen upplevdes av många som påfrestande och begränsande. Behovet av information var individuellt. Stöd var för många patienter det som underlättade behandlingen mest. Sjuksköterskan behöver därför individanpassa vården utifrån patientens behov och resurser. / Introduction: Patients with hematological cancer can undergo stem cell transplantation as a treatment to get new blood-forming stem cells. The goal with transplantation and chemotherapy is survival and to cure malignancy.  Purpose: To study the experience of patients with hematological cancer undergoing hematopoietic stem cell transplantation.  Method: A descriptive literature review where 11 qualitative studies have been reviewed. The literature search was made via the databases CINAHL and PubMed. The quality analysis is based on the quality review template by SBU. The result analysis was conducted according to Friberg’s five-step model.  Results: Many negative aspects emerged, but there were also positive experiences in some of the subcategories. Many of the participants experienced that side effects were limiting, including fatigue that could remain and affect them months after treatment. Several participants felt scared of dying or falling ill again. Support from relatives, nursing staff and patients was an important part to cope with treatment. Protective isolation was experienced by most as difficult, but could for some feel like a safe environment. A predominant part of the participants had the need of being well informed before and during stem cell transplantation.  Conclusion: Patients undergoing stem cell transplantation because of hematological cancer are affected by the treatment in several ways, mostly negative and fear was common. Side effects also affected returning to everyday life. Protective isolation was experienced as stressful and limiting. The need of information was individual. Social support was for many patients what helped to ease treatment most. Nurses therefore need to personalize the care of these patients, from their needs and resources.

Aim: To determine if a significant relationship exists between bloodless medicine practices and decreased infection rates in oncology patients following hematopoietic stem cell transplantation by performing a literature review. Background: It is not uncommon for healthcare professionals to encounter Jehovah's Witnesses (JW) seeking medical treatment in the acute care hospital setting and outpatient clinics alike. However, JW's pose a unique challenge to healthcare providers. Their refusal of blood transfusions makes them a population of interest within the medical community. The refusal of blood transfusions also poses a serious challenge to successful treatment in oncology JW patients, and many hospitals will refuse to perform a procedure as complex yet beneficial as a hematopoietic stem cell transplant in this population. Methods: An extensive electronic literature search in the CINAHL Plus database was completed and included the keywords infection, blood transfusion, stem cell transplant, bloodless medicine, Jehovah's Witnesses, and transfusion reactions. The available literature was carefully examined for interventions performed and compared for ultimate results to be finalized as a written report. Significance: The results of this research can not only optimize healthcare for the population of Jehovah's Witnesses, but also assist in reduced blood transfusions and improved cost management in all patients with a cancer diagnosis. Conclusions: All studies concluded that autologous hematopoietic stem cell transplantation can be performed safely without the use of blood products. Their conclusion was based off of the data they collected following patients post-stem cell transplant. More research is needed to explore outcomes in this population as a result of blood transfusion refusal following stem cell transplantation in comparison with those who receive blood transfusion support.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23782号 / 医博第4828号 / 新制||医||1057(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 羽賀 博典, 教授 波多野 悦朗, 教授 溝脇 尚志 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM