脐带间充质干细胞最新进展

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1、UMBILICAL CORD STEM CELLSJayanti Tokas1, Puneet Tokas2, Rubina Begum1, Shailini Jain3 and Hariom Yadav31Department of Biotechnology, JMIT, Radaur, Haryana, India2KITM, Kurukshetra, Haryana, India3NIDDK, National Institute of Health, Bethesda, MD 20892, USAEmail: Umbilical cord stem cells (UCS cells)

2、Also Known as Whartons JellyAdult stem cells of infant originIsolated prior to/ immediately following birthHaematopoietic stem cells (Majority)100,000 stem cells per mL in UCBAlternate to bone marrow stem cellsUmbilical cord stem cellsThree important functions of UCS cells:- Plasticity: Potential to

3、 change into other cell types like nerve cells - Homing: To travel to the site of tissue damage - Engraftment: To unite with other tissues Cord blood Vs Bone MarrowCord BloodCollection is non-invasive, painless, and poses no risk to the donor.Greater HLA compatibility due to decreased functionality

4、of fetal lymphocytes.Graft versus Host Disease (GVHD) is reduced to 10% due to the absence of antibodies in the stem cells.Units are processed and ready for transplant.Significantly less expensiveBone Marrow Collection is invasive and painful. Must be performed in a hospital surgical setting.Due to

5、the maturity of the stem cells, it requires a greater HLA match to perform a transplant.Serious GVHD occurs in 60% of all unrelated Bone Marrow transplantsBone Marrow is dependent on donor participation. ApplicationsHematopoietic cell transplantation (HCT) of umbilical cord origin is curative for ma

6、lignant and nonmalignant diseases like Fanconis anemia, aplastic anemia, leukemias, metabolic and other congenital disorders.HLA mismatch may be better tolerated in the UCBT setting than Bone Marrow Transplantation.Regenerative medicine in cardiology Transplanted UCSC provide benefit in cardiac func

7、tion recovery after acute myocardial infarction in rats (Kai Hong et. al., 2007)Some UCSC express cardiac troponin-T, von Willebrand factor, and smooth muscle actin, indicating regeneration of damaged myocardium by cardiomyocytic, endothelial, and smooth muscle differentiation of UCDS cells in the i

8、nfarcted myocardiumIschemic vascular disease Buergers disease - characterized by a combination of acute inflammation and thrombosis (clotting) of the arteries and veins in the hands and feet leading to pain, ulceration and necrosis of extremitiesUmbilical cord blood (UCB)-derived mesenchymal stem ce

9、lls (MSCs) were transplanted to HLA matched patientsAfter transplantation ischemic rest pain disappeared, necrotic skin lesions were healed within 4 weeks.Metabolic storage diseases Hurler syndrome- Severe form of mucopolysaccharidosis type I, causes progressive deterioration of the CNS and death in

10、 childhood.Transplantation of umbilical cord blood stem cells improved neurocognitive performance and decreased somatic features of Hurlers syndromeHemoglobinopathies Fanconi anemia- Umbilical cord blood cells from HLA matched sibling used. The engraftment is slow. There is no graft-versus-host dise

11、ase. Malignant diseasesAcute leukemia- Cord blood from an unrelated donor was found to be useful for adults with acute leukemia who lack an HLA-matched bone marrow donor (Wall et. al., 2005)Neurological disorders UCMS cells transplanted into the brains of hemiparkinsonian rats that were not immune-s

12、uppressed. Neural transplantation showed to ameliorate functional and cognitive deficits in animal models of neurological disorders and has reached clinical trials in Parkinson disease, Huntington disease and stroke. Cellular vehicles for gene therapyUmbilical cord stem cells can be stably transduce

13、d using Retroviral vectors for necessary genetic correction and can be used for transplantationFuture applications In autoimmune diseases, where there has been some success with autologous transplantation and the low risk of graft-versus-host disease makes cord blood transplantation attractive.In el

14、derly patients with a high risk of graft-versus-host disease In theory, in an HIV patient, an allogenic umbilical cord stem cell vaccine may be used to replace the HIV infected hematopoietic stem cells. Cord Blood banking Cord blood banking involves RecruitmentConsentTesting of maternal donors Colle

15、ctionProcessingCryopreservationTestingReleasing cord blood unit to transplant centreTests for UCBMeasurement of Viability (Flowcytometry)Blood TypingCounting of blood cellsCount of CD34+ Stem cellsCFU assayAnit-HIVCMVAnti HBcAnti HCVHBsAgEx vivo expansionLimitations of cord blood stem cellsLimitatio

16、ns of cord blood stem cells for allogeneic transplantationlDelayed platelet engraftment lDelayed neutrophil engraftmentLimitations of cord blood as a stem cell sourcelLimited amount of source materiallSame donor not available for repeated doseConclusionsUnlimited source of stem cells from biological

17、 wasteCollection of cord stem cells is painless Collection of cord stem cells is risk free to mother and babyCord blood stem cells have a greater ability to differentiate into other cell typesThese cells have longer growth potential and have been shown to have a greater rate of engraftmentCord blood

18、 stem cells are much more tolerant to HLA tissue mismatching than bone marrow therefore leading to lower rate of GVHDCord stem cells are not exposed to the toxins and radiations (we experience in everyday life)Cord blood stem cells are being used in the treatment of 40 medical conditions with over 72 potential disease targetsResearch should be oriented towards prolonging their storage and enhancing their expansionConclusions

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