published_or_final_version / Anatomy / Master / Master of Research in Medicine

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 6 uppsatser.

Thesis (M. Res.(Med.))--University of Hong Kong, 2008. / Includes bibliographical references (p. 91-117)

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1994. / Vita. Abstract. Includes bibliographical references. Also available via the Internet.

No description available.

Tsang Kam Sze Kent. / "March 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 277-339). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Lau Fung Yi. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 107-130). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Lam Audrey Carmen. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 166-195). / Abstracts in English and Chinese. / Acknowledgements --- p.vi / Publications --- p.vii / Abbreviations --- p.x / Abstract --- p.xiii / Chapter Chapter One - --- Introduction --- p.1 / Chapter Section 1.1 --- Hematopoietic Stem Cells --- p.1 / Chapter 1.1.1 --- Hematopoiesis --- p.1 / Chapter 1.1.2 --- Hematopoietic Stem and Progenitor Cells --- p.1 / Chapter Section 1.2 --- Stem Cell Transplantation --- p.4 / Chapter 1.2.1 --- Stem Cell Transplantation --- p.4 / Chapter 1.2.2 --- Sources of Hematopoietic Stem Cells for Transplantation --- p.4 / Chapter 1.2.3 --- Cord Blood as a Source of Hematopoietic Stem Cells --- p.6 / Chapter 1.2.3.1 --- Advantages of Cord Blood Transplant --- p.6 / Chapter 1.2.3.2 --- Disadvantages of Cord Blood Transplant --- p.7 / Chapter Section 1.3 --- Ex Vivo Expansion --- p.8 / Chapter 1.3.1 --- Optimization of Expansion Conditions --- p.10 / Chapter 1.3.1.1 --- CD34+ Cell Selection --- p.10 / Chapter 1.3.1.2 --- Cytokines --- p.11 / Chapter 1.3.1.2.1 --- Thrombopoietin --- p.12 / Chapter 1.3.1.2.2 --- Stem Cell Factor --- p.14 / Chapter 1.3.1.2.3 --- Flt-3 Ligand --- p.15 / Chapter 1.3.1.2.4 --- Granulocyte-Colony Stimulating Factor --- p.16 / Chapter 1.3.1.2.5 --- Interleukin-3 --- p.17 / Chapter 1.3.1.2.6 --- Interleukin-6 --- p.18 / Chapter 1.3.1.2.7 --- Comparison of Flt-3 Ligand and Stem Cell Factor --- p.20 / Chapter 1.3.1.3 --- Culture Medium --- p.20 / Chapter 1.3.2 --- Mannose-Binding Lectin --- p.22 / Chapter 1.3.3 --- Ex Vivo Expansion for Clinical Transplantation --- p.23 / Chapter Section 1.4 --- Non-Obese Diabetic/Severe Combined Immunodeficient Mouse Transplantation Model --- p.29 / Chapter Chapter Two - --- Objectives --- p.32 / Chapter Chapter Three - --- Materials and Methodology --- p.34 / Chapter Section 3.1 --- Collection of Cord Blood Samples / Chapter Section 3.2 --- Cryopreservation and Thawing of Cord Blood --- p.34 / Chapter Section 3.3 --- Enrichment of CD34+ Cells --- p.35 / Chapter Section 3.4 --- Ex Vivo Expansion --- p.38 / Chapter 3.4.1 --- Effects of Flt-3 Ligand and stem Cell Factor on the Expansion of Megakaryocytic Progenitor Cells --- p.39 / Chapter 3.4.1.1 --- Ex Vivo Expansion of Cord Blood CD34+ Cells with Flt-3 Ligand or Stem Cell Factor --- p.39 / Chapter 3.4.1.2 --- Flt-3 Receptor Assay --- p.40 / Chapter 3.4.2 --- Effects of Mannose-Binding Lectin on the Ex Vivo Expansion of Hematopoietic Stem and Progenitor Cells --- p.41 / Chapter 3.4.2.1 --- Ex Vivo Expansion of Cord Blood CD34+ Cells with Mannose-Binding Lectin --- p.41 / Chapter 3.4.2.2 --- Effects of Mannose-Binding Lectin on the Preservation of Early Stem and Progenitor Cells --- p.41 / Chapter 3.4.2.3 --- Transplantation of Expanded Cells into NOD/SCID Mice --- p.42 / Chapter 3.4.3 --- "Optimization of Culture Duration, Culture Media, Autologous Plasma and Cytokine Combinations for the Preclinical Ex Vivo Expansion of Hematopoietic Stem and Progenitor Cells" --- p.42 / Chapter 3.4.3.1 --- "Comparison of Culture Duration, Culture Media and Cytokine Combinations" --- p.42 / Chapter 3.4.3.2 --- Effects of Autologous Cord Blood Plasma --- p.43 / Chapter 3.4.3.3 --- Effects of Flt-3 Ligand and Dosage of Thrombopoietin and Stem Cell Factor --- p.43 / Chapter 3.4.3.4 --- Transplantation of Expanded Cells into NOD/SCID Mice --- p.44 / Chapter Section 3.5 --- Progenitor Colony-Forming Assays --- p.44 / Chapter 3.5.1 --- Colony-Forming Unit Assay --- p.44 / Chapter 3.5.2 --- Colony Forming Unit Megakaryocyte --- p.46 / Chapter 3.5.3 --- Calculations of CFU --- p.46 / Chapter Section 3.6 --- Flow Cytometry Analysis --- p.47 / Chapter Section 3.7 --- Transplantation of Non-Obese Diabetic/Severe Combined Immunodeficient Mice --- p.48 / Chapter Section 3.8 --- Assessment of Human Cell Engraftment in Transplanted NOD/SCID Mice --- p.49 / Chapter 3.8.1 --- Flow Cytometry Analysis --- p.49 / Chapter 3.8.2 --- PCR Analysis --- p.50 / Chapter Section 3.9 --- Statistical Analysis --- p.52 / Chapter Chapter Four - --- Effects of Flt-3 Ligand and Stem Cell Factor on the Expansion of Megakaryocytic Progenitor Cells --- p.53 / Chapter Section 4.1 --- Results --- p.53 / Chapter 4.1.1 --- Ex Vivo Expansion of CD34+ Cells --- p.53 / Chapter 4.1.2 --- Identification of Flt-3 Receptors --- p.55 / Chapter Section 4.2 --- Discussion --- p.55 / Chapter Chapter Five- --- Effects of Mannose-Binding Lectin on the Ex Vivo Expansion of Hematopoietic Stem and Progenitor Cells --- p.68 / Chapter Section 5.1 --- Results --- p.68 / Chapter 5.1.1 --- Ex Vivo Expansion of CD34+ Cells with Mannose-Binding Lectin --- p.68 / Chapter 5.1.2 --- Effects of Mannose-Binding Lectin on the Preservation of Early Stem and Progenitor Cells --- p.72 / Chapter 5.1.3 --- Transplantation of Expanded Cells into NOD/SCID Mice --- p.75 / Chapter Section 5.2 --- Discussion --- p.76 / Chapter Chapter Six - --- "Optimization of Culture Duration, Culture Media, Autologous Plasma and Cytokine Combinations for the Preclinical Ex Vivo Expansion of Hematopoietic Stem and Progenitor Cells" --- p.111 / Chapter Section 6.1 --- Results --- p.111 / Chapter 6.1.1 --- Kinetics of Expansion --- p.111 / Chapter 6.1.2 --- Assessment of Culture Media --- p.113 / Chapter 6.1.3 --- Effects of Autologous Cord Blood Plasma --- p.115 / Chapter 6.1.4 --- Effects of Granulocyte-Colony Stimulating Factor --- p.117 / Chapter 6.1.5 --- Effects of Interleukin-6 --- p.118 / Chapter 6.1.6 --- Effects of Increased Dosage of Thrombopoietin and Stem Cell Factor --- p.119 / Chapter 6.1.7 --- Effects of Flt-3 Ligand --- p.120 / Chapter 6.1.8 --- Transplantation of Expanded Cells into NOD/SCID Mice --- p.121 / Chapter Section 6.2 --- Discussion --- p.123 / Chapter Chapter Seven- --- General Discussion and Conclusion --- p.163 / Bibliography --- p.166

Human mesenchymal stem cells (MSCs) are being largely studied for their differentiation potential and immunological properties. In the present study, we evaluated the ability to reliably differentiate mesenchymal lineages into hepatocyte-like cells both in vitro and in vivo. For this purpose, we handled several tissue sources and compared typical MSCs from bone marrow (BM) or umbilical cord, to liver-derived mesenchymal-like cells and to fibroblasts. We observed that hepatocyte differentiation of BM-MSCs was incomplete and variable with elective expression of some specific markers. These mesenchymal-derived hepatocyte-like cells (MDHLCs) were also chimerical in their phenotype as they expressed mesenchymal markers while these were down-regulated. We therefore designed differentiation cocktails with an aim to improve MDHLC phenotype and some unexpected results were obtained with LIF cytokine whose action on stem cells for hepatocyte differentiation was not documented. Nevertheless, we observed a limitation in the acquisition yield of hepatic features. Furthermore, the hepatocytelike phenotype of MDHLCs completely disappeared when the cells were incubated into growth medium. However, we showed that hepatic functionality of these cells, as urea secretion and gluconeogenesis, could be increased under specific conditions, suggesting the potential to improve MDHLC phenotype. In vivo, MSCs were able to express hepatic markers into SCID-mice livers while their chimerical phenotype remained. In contrast, MDHLCs down-regulated their hybrid phenotype after transplantation suggesting a beneficial influence of in vitro differentiation step. MSCs were also able to engraft and even partially differentiate into wild-type mice which was a strong argument for their low immunogenicity. Surprisingly, fibroblasts showed highly similar potential than MSCs to differentiate into hepatocyte-like cells both in vitro an in vivo and these results underlined the difficulty to accurately distinguish between both cell types using current techniques. Umbilical cord-derived stem cells (UCMSCs) and adult-derived human liver stem cells (ADHLSCs) were different in nature and displayed a native hybrid phenotype while their differentiation allowed high levels of hepatocyte-like feature acquisition. Together all these data suggest the current possibility to engineer mesenchymal-derived hepatocyte-like cells owning specific features acquisition while remaining limited in their commitment. This highlights the need for further investigations to evidence the usefulness of these mesenchymal lineages for liver cell therapy.