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:1Umbilical cord stem cells(UCS cells)Also Known as W

2、hartons 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 cells2Umbilical cord stem cellsThree important functions of UCS cells:-Plasticity:Potential to change into other

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

4、t 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 the maturity of the stem cell

5、s,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.4ApplicationsHematopoietic cell transplantation(HCT)of umbilical cord origin is curative for malignant and nonmalignant diseases

6、 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.5Regenerative medicine in cardiology Transplanted UCSC provide benefit in cardiac function recovery after acute myocardia

7、l 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 infarcted myocardium6Ischemic vascular disea

8、se 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 cells(MSCs)were transplanted to HLA matched patien

9、tsAfter transplantation ischemic rest pain disappeared,necrotic skin lesions were healed within 4 weeks.7Metabolic storage diseases Hurler syndrome-Severe form of mucopolysaccharidosis type I,causes progressive deterioration of the CNS and death in childhood.Transplantation of umbilical cord blood s

10、tem cells improved neurocognitive performance and decreased somatic features of Hurlers syndrome8Hemoglobinopathies Fanconi anemia-Umbilical cord blood cells from HLA matched sibling used.The engraftment is slow.There is no graft-versus-host disease.9Malignant diseasesAcute leukemia-Cord blood from

11、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)10Neurological disorders UCMS cells transplanted into the brains of hemiparkinsonian rats that were not immune-suppressed.Neural transplantation showed to ameliorate fu

12、nctional and cognitive deficits in animal models of neurological disorders and has reached clinical trials in Parkinson disease,Huntington disease and stroke.11Cellular vehicles for gene therapyUmbilical cord stem cells can be stably transduced using Retroviral vectors for necessary genetic correcti

13、on and can be used for transplantation12Future 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 elderly patients with a high risk of graft-versus-host dis

14、ease In theory,in an HIV patient,an allogenic umbilical cord stem cell vaccine may be used to replace the HIV infected hematopoietic stem cells.13Cord Blood banking Cord blood banking involves RecruitmentConsentTesting of maternal donors CollectionProcessingCryopreservationTestingReleasing cord bloo

15、d unit to transplant centre14Tests for UCBMeasurement of Viability(Flowcytometry)Blood TypingCounting of blood cellsCount of CD34+Stem cellsCFU assayAnit-HIVCMVAnti HBcAnti HCVHBsAgEx vivo expansion15Limitations of cord blood stem cellsLimitations of cord blood stem cells for allogeneic transplantat

16、ionlDelayed platelet engraftment lDelayed neutrophil engraftmentLimitations of cord blood as a stem cell sourcelLimited amount of source materiallSame donor not available for repeated dose16ConclusionsUnlimited source of stem cells from biological wasteCollection of cord stem cells is painless Colle

17、ction 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 engraftment17Cord blood stem cells are much more tolerant to HLA tissue mi

18、smatching 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 expansionConclusions1819