動物器官移植

1、試想，如果一個人的身體里被安進一顆豬的心臟或者換一個猩猩的肝，他會做何感想，他的生命還會延續(xù)嗎？日前，大部分澳大利亞人表示，假如自己瀕臨死亡時，將愿意嘗試接受動物的器官移植。這個說法聽起來似乎有點不可思議，在醫(yī)學發(fā)達的今天，人體究竟能否移植動物器官？移植后會和人體產(chǎn)生排斥嗎？移植器官來源的最佳方式是什么呢？帶著一系列問題，本報記者專程采訪了在我國器官移植領(lǐng)域有多年經(jīng)驗的管德林教授。器官移植面臨的最大問題就是供體器官奇缺，很多人在等待中死去。管德林教授是我國器官移植的權(quán)威，在談到器官移植的問題時，他先給記者講了一件讓他終生難忘的事。1997年的秋天，他在澳大利亞做訪問期間，有位只有26歲的姑娘，

2、因為酒后駕車撞到了一棵大樹上。當時她就發(fā)生了腦死亡，只能靠插管維持呼吸和心跳，但她的親屬告訴醫(yī)生愿意將器官捐獻。管教授回憶說：“當時我們?nèi)×怂男呐K、肺、肝、兩個腎臟、胰腺，一共七個臟器，第二天就給6個病人實施移植手術(shù)。特別巧的是，過了幾天后，我們在醫(yī)院的院子里，碰到6個病人在一起聊天，他們正好是姑娘救活的那幾個人。他們曾經(jīng)瀕臨死亡，現(xiàn)在卻因為一個姑娘的臟器，全都活了下來。你不覺得這很神奇嗎？”據(jù)介紹，一個病人的死亡原因常常只是某個臟器損壞，而非所有臟器都有問題，所以在這個時候，做器官移植手術(shù)就可以使很多患者的生命延續(xù)下去。經(jīng)過幾代人的努力，上個世紀50年代，美國的一位科學家實現(xiàn)了人類的這個夢

3、想。1954年，第一例腎移植手術(shù)由美國醫(yī)生約瑟夫·默里成功進行。迄今為止，全世界僅心、肝、腎人體三大器官的移植已經(jīng)達到50萬例。我國器官移植從上個世紀60年代開始，雖然開展比國外晚，但進展卻很快。目前，器官移植面臨的最大問題就是供體器官奇缺，很多人在等待中死去。全世界目前等待合適的供體器官做移植手術(shù)的病人有30萬人。為了促進器官移植的快速發(fā)展，挽救更多人的生命，科學家一直在尋求更多更好的供體器官。就供體器官的來源和質(zhì)量問題，當然是同種器官(即人的器官)最好，但在供不應(yīng)求的局勢下，專家們把探索的方向轉(zhuǎn)向了動物器官。人類最早的嘗試是把羊的臟器移植到人體內(nèi)，但由于當時對免疫學方面的經(jīng)驗缺乏

4、，這個器官很快就被排斥掉了。之后，世界上很多科學家都分別做過嘗試，把狗、豬、猴子的臟器試圖移植到人體內(nèi)，但這些嘗試最終都沒有成功。據(jù)管教授介紹，“目前國內(nèi)還沒有一例把動物器官移植給人的，但世界上第一個把動物器官移植到人體內(nèi)的是位中國人，他就是美籍華裔馮宙麟博士，他成功地把狒狒的肝移植到人身上，雖然那人只存活了一個月，但這至少是種新嘗試?！?眾所周知，器官移植的最大瓶頸在于排斥反應(yīng)。人和人之間還要發(fā)生排斥，那么動物和人之間移植后會發(fā)生排斥嗎？答案是肯定的，假如動物的臟器不經(jīng)過特殊處理，移植到人體后幾分鐘內(nèi)就會發(fā)生超級排斥。因為人類經(jīng)過億萬年時間生存下來后，有一套自己健全的生態(tài)系統(tǒng)，絕不允許外來種

5、族進行干擾。所以一旦有“外物”侵入，人體自身就會產(chǎn)生大量抗體、補體，這些東西被激活后就把所有血管堵塞，此時這個臟器就會立即變黑壞死，不能發(fā)揮任何作用。移植動物器官的想法由來已久，但感染動物病毒的隱患還未能解決?？茖W家仍在立志解決排斥的難題，“但這不是最主要的，最主要的問題是擔心動物的病毒會傳染給人類”。管教授在評價移植動物器官時，臉上露出了幾分擔憂。他說：“據(jù)科學家報告分析，人類現(xiàn)在談虎色變的幾種超級病毒，都是從動物體內(nèi)傳染給人的。比如，艾滋病病毒最初就是非洲猩猩傳染給人的。幾億萬年前，猩猩內(nèi)部也曾流行艾滋病，那時候大部分猩猩死亡，只有一小部分猩猩繼續(xù)留存下來，而它們體內(nèi)就會有耐病毒的抗體，這

6、種病毒不會在它們體內(nèi)發(fā)作。但后來這個病毒傳染給人后，就開始了新一輪的猛烈攻擊。還有禽流感等其他病毒，這些病毒一旦傳染給人類，我們目前根本沒有辦法治療。一旦這些病毒在人體內(nèi)適應(yīng)下來，造成人間傳播，那全世界死幾十億人都是可能的，這個后果相當嚴重。”為了避免傳染動物的病毒，現(xiàn)在英、美等國家已經(jīng)在法律上開始限制做這方面的研究。瑞士在2001年7月頒布新規(guī)定，允許有條件地將動物器官、組織和細胞移植于人體。但瑞士政府嚴禁向人體移植靈長類動物器官，因為靈長類動物與人類種群過于接近，他們擔心移植后感染動物病毒的風險性比較大。 不過就在人們失望之余，事情似乎又有了轉(zhuǎn)機。2000年8月底，美國有科研人員宣布，他們

7、已經(jīng)培養(yǎng)出一種新型轉(zhuǎn)基因豬，豬體內(nèi)固有的豬逆轉(zhuǎn)錄病毒不會傳遞給人。這一研究結(jié)果似乎給移植動物器官的安全做了某種保證，但研究人員也謹慎地說，他們還不知道PERV不感染人細胞的深層機理，而且PERV的無感染性還需通過活體動物試驗才能進一步確認。   解決缺少供體器官的最佳辦法，是鼓勵人們自愿捐獻和出臺相應(yīng)法律規(guī)定。有專家表示，有朝一日人們或許可以解決傳染病毒的問題，最終實現(xiàn)無風險異種器官移植。但在目前情況下，解決缺少移植器官供體的最佳辦法，還是鼓勵人們器官捐獻和出臺提取器官的有關(guān)法律規(guī)定。對此，管德林教授也表示了贊同意見。他說：“國內(nèi)去年做了將近5000例腎臟移植手術(shù)，但親屬提供臟器卻非

8、常少，在國內(nèi)不到1%的比例。這個數(shù)字說明老百姓對這個問題認識不足。在中國，大部分的器官捐獻都是父母捐給子女的，很少有兒女捐給父母的，有的即使捐獻，父母也拒絕接受。實際上這種思想太傳統(tǒng)，從醫(yī)學角度來講，子女捐給父母最好，因為他們的腎臟很年輕，成活率會很高。”但傳統(tǒng)的觀念使很多人認為，捐獻人的身體健康會受到嚴重影響，其實不然，管教授說“人的腎臟只要有1/7，就能發(fā)揮正常功能正常生活。”雖然我國器官移植方面的技術(shù)已經(jīng)接近國際水平，但是在立法領(lǐng)域，我國還遠遠落后于世界發(fā)達國家?！艾F(xiàn)在最關(guān)鍵的就是沒有法律的保護，有人愿意捐獻，但醫(yī)院也不敢要?！惫芙淌谥v了一件他親歷的事情，“以前我在朝陽醫(yī)院工作時，有個姑

9、娘找到我，懇求我答應(yīng)他爸爸一個愿望。原來他父親得了腦腫瘤，他想把自己的臟器捐獻。后來我請示了上級，最后因為沒有法律保障，而不敢隨便接受。所以老人的這個愿望也沒能實現(xiàn)。”在英、法、美、加拿大等國家，包括我國香港地區(qū)對器官移植都有相關(guān)法律規(guī)定。在美國，每個人考駕駛執(zhí)照時，都會有一欄內(nèi)容需本人填寫。這欄內(nèi)容就是一旦你發(fā)生意外，造成腦死亡，自愿把臟器捐獻。當車禍發(fā)生后，警察只要一劃卡就知道個人捐獻的情況，隨時可以通知醫(yī)院來取臟器。管教授說：“腦死亡的人大腦皮層和腦干已經(jīng)全部死亡，沒有呼吸。腦死亡的病人活不到一個星期，這個時期正好是捐獻的最佳時機。”將動物的器官植入人體，即便是為了拯救生命，仍有許多人表

10、示無法接受。然而，近日的一項調(diào)查顯示，澳大利亞人對動物器官移植并沒有太多成見，他們愿意接受“異族”的器官，因為志愿者捐贈的人體器官實在是不夠用。 據(jù)報道，澳大利亞器官移植協(xié)會最近發(fā)起了一項旨在研究人們對動物器官接受程度的調(diào)查。調(diào)查結(jié)果發(fā)現(xiàn)，大部分澳大利亞人表示可以接受醫(yī)生在他們?yōu)l臨死亡的時候?qū)λ麄冞M行動物器官移植。目前，澳洲醫(yī)學界使用最多的非人體器官是豬心和珊瑚蟲骨骼。 專家說，醫(yī)學界之所以下大力氣開拓新的器官移植領(lǐng)域，實在是迫于現(xiàn)實的嚴峻。眼下，在需要進行器官移植的病人中，有五分之一的人因等不到適合的器官而撒手人寰。此前，大部分人認為，澳大利亞每年新捐贈給醫(yī)院供手術(shù)用的人體器官至少有500至

11、5000個，但實際上，去年僅有179人表示愿意捐贈，遠遠低于預(yù)期。有調(diào)查顯示，有一多半的澳大利亞人從未與家人談及死后捐贈器官的事宜。 澳大利亞器官移植協(xié)會新南威爾士分會的主席安東尼·哈丁在評價動物器官移植時說：“澳大利亞現(xiàn)在急需適合的活器官，所以任何可能的方法都要試一試”。(高雯)CLINICAL XENOTRANSPLANTATION: CURRENT PROGRESS, PROBLEMS AND SOLUTIONS/Li Youping, Ma Yukui, He Qiuming. Transplant Immunology Laboratory, First Universit

12、y Hospital, West China University of Medical Sciences, Chengdu, P. R. China 610041AbstractXenotansplantation has become a global focus because it may solve the formidable problems in allotransplantation, that is, the donor source. Hitherto clinical xenotransplantion has been in the stage of research

13、 with limited cases and unsatisfactory results. The difficulties which hinder the progress of xenotransplantation include: the ideal animal donor has not been found, it is rather difficult to control the rejections (hyperacute rejection, acute vascular rejection, perhaps acute cellular rejection and

14、 chronic rejection) after xenotransplantation compared with those after allotransplantation, some animal diseases might be transmitted to and do harm to human recipients, even the community. It is still unknown whether the functions of animal organs can substitute those of human organs permanently.

15、Transgenic pigs on research and various measurements to suppress humoral and cellular immunity may be helpful in overcoming the problems of xenogeneic rejections. Animal diseases should be prevented, screened and treated, and animal models should be established to study the possibility of satisfacto

16、ry working of animal organs in human body before clinical xenotransplantation is widely practised.Key words Clinical xenotransplantationBreeding of inbred large aminalTrangenic large animalPrevention and treatment of animal diseaseFunction of xenograft異種移植是最終解決全球性供器官嚴重短缺問題的最有效途徑之一。盡管器官移植研究從異種移植開始嘗試，

17、但至今發(fā)展卻遠遠落后于同種異體移植，其根本原因在于：現(xiàn)有動物中究竟哪種動物的臟器功能可與人替換?異種排斥反應(yīng)可以被克服?人畜共患疾病可以被篩檢防治?其遺傳具有穩(wěn)定性，經(jīng)近交培育后可供基因改造?用于臨床移植在產(chǎn)量、價格、規(guī)?；a(chǎn)和倫理方面相對最可行?至今尚無明確答案。現(xiàn)就60年代以來全球臨床異種大動物器官移植的實例、暴露和面臨的問題，以及針對這些問題的探索和研究進行綜述，希望有助于尋求解決的辦法。雅虎科學2005年9月12日訊：據(jù)9月11日都柏林媒體報道，一位科學家本周稱，由于人體捐獻器官的嚴重不足，在未來的幾年里，把動物器官移植給人體可能將實施。就在近幾年，許多潛在的免疫學難題被克服了，如身

18、體器官移植的排異反應(yīng)等，這也意味著把器官從一個物種身上移植到另一個物種身上的可能性將成為現(xiàn)實。    目前世界上約有25萬病人等待做器官移植手術(shù)，但是每年有機會接受這種手術(shù)治療的患者只有約5萬人左右。因為捐獻的器官只有這么多。而異種移植，即使用另外一個物種的器官、組織或細胞，被認為是最好的解決問題的辦法。    為了尋找這種跨物種器官移植手術(shù)的奧妙，科學家們先在動物之間進行了類似的實驗。英國劍橋大學的科學家自1992年開始飼養(yǎng)世界上第一群心臟中含有人基因的豬，科學家是將豬卵細胞中植入人的一種基因后培養(yǎng)出這種豬的。在豬長成后，科學家將豬

19、心臟植入猴子體內(nèi)。實驗表明，將豬心臟植入猴子體內(nèi)后，猴子體內(nèi)幾乎不產(chǎn)生排異反應(yīng)，植入豬心臟的猴子手術(shù)后平均存活時間為40天。此后，英國科學家決定選擇4到5名患者進行豬心臟移植手術(shù)。    科學家說，存在于豬組織內(nèi)的病毒似乎不會感染人類，它繞開了一個在實踐中阻礙給人體移植豬器官的主要障礙。另外，科學家之所以對豬情有獨鐘，因為它們與人類有許多相似之處。豬的心臟與人的心臟大小相同，其管道分布和動力輸出也相類似。此外，豬的心臟只需經(jīng)過很少量的基因工程處理，就能與人類的免疫系統(tǒng)相兼容。    因此豬的器官被認為是進行移植的比較理想的來源，因為它

20、們的大小同人類差不多，而且有著同人類類似的生理結(jié)構(gòu)。科學家們現(xiàn)在正致力于培養(yǎng)出有合適基因工程的豬，這種豬的組織不會同人體內(nèi)的免疫系統(tǒng)產(chǎn)生排異反應(yīng)。    但科學家們目前還不知道“豬身上的內(nèi)生長逆轉(zhuǎn)錄酶病毒(一種病毒，大多數(shù)會產(chǎn)生含有核糖核酸和逆轉(zhuǎn)錄酶的腫瘤，包括引起愛滋病的病毒)”是否也會隨器官移植轉(zhuǎn)移到人體內(nèi)，或者這種病毒是否會發(fā)生變異并引起新的疾病。這也是科學家們最關(guān)心的問題。但也有理由充分相信這并不是一個大的難題。現(xiàn)在科學家們會延遲異種器官對人體的移植，直到這些問題被全都克服?？茖W家真正開始臨床實驗可能要等到5年以后，而接受異種器官移植的病人每天的日常生活都

21、將得到監(jiān)控。XenotransplantationFrom Wikipedia, the free encyclopediaJump to: navigation, searchXenotransplantation (xeno- from the Greek meaning "foreign") is the transplantation of living cells, tissues or organs from one species to another, such as from pigs to humans (see medical grafting). S

22、uch cells, tissues or organs are called xenografts or xenotransplants. In contrast, the term allotransplantation refers to a same-species transplant. Human xenotransplantation offers a potential treatment for end-stage organ failure, a significant health problem in parts of the industrialized world.

23、 It also raises many novel medical, legal and ethical issues.1 A continuing concern is that pigs have shorter lifespans than humans: their tissues age at a different rate. Disease transmission (xenozoonosis) and permanent alteration to the genetic code of animals are also causes for concern. There a

24、re few published cases of successful xenotransplantationPotential future usesBecause there is a worldwide shortage of organs for clinical implantation, about 60% of patients awaiting replacement organs die on the waiting list. Recent advances in understanding the mechanisms of transplant rejection h

25、ave brought science to a stage where it is reasonable to consider that organs from other species, probably pigs, may soon be engineered to minimize the risk of serious rejection and used as an alternative to human tissues, possibly ending organ shortages. Other procedures, some of which are being in

26、vestigated in early clinical trials, aim to use cells or tissues from other species to treat life-threatening and debilitating illnesses such as cancer, diabetes, liver failure and Parkinson's disease. If vitrification can be perfected, it could allow for long-term storage of xenogenic cells, ti

27、ssues and organs so that they would be more readily available for transplant.Xenotransplants could save thousands of patients waiting for donated organs. The animal organ, probably from a pig or baboon could be genetically altered with human genes to trick a patients immune system into accepting it

28、as a part of its own body. They have re-emerged because of the lack of organs available and the constant battle to keep immune systems from rejecting allotransplants. Xenotransplants are thus potentially a more effective alternative.Also, xenotransplantation of ovarian tissue into immunodeficient nu

29、de mice or SCID mice is already used in research to study the development of ovarian follicles.3 Mature follicles have developed, even after use of cryopreserved ovarian tissue.4 Both host and graft vessels contribute to the revascularization of xenografted human ovarian tissue in a mice.5editPotent

30、ial future animal organ donorsSince they are the closest relatives to humans, nonhuman primates were first considered as a potential organ source for xenotransplantation to humans. Chimpanzees were originally considered to be the best option since their organs are of similar size, and they have good

31、 blood type compatibility with humans. However, since chimpanzees are listed as an endangered species, other potential donors were sought out. Baboons are more readily available, however they are also not practical as potential donors. Problems include their smaller body size, the infrequency of blo

32、od group O (the universal donor), their long gestation period, and they typically produce few offspring. In addition, a major problem with the use of nonhuman primates is the increased risk of disease transmission, since they are so closely related to humans. 6 Pigs are currently thought to be the b

33、est candidates for organ donation. The risk of cross-species disease transmission is decreased because of their increased phylogenetic distance from humans .7 They are readily available, their organs are anatomically comparable in size, and new infectious agents are less likely since they have been

34、in close contact with humans through domestication for many generations .8. Current experiments in xenotransplantation most often use pigs as the donor, and baboons as human models.editBarriers and issueseditImmunologic BarriersTo date no xenotransplantation trials have been entirely successful due

35、to the many obstacles arising from the response of the recipients immune system. This response, which is generally more extreme than in allotransplantations, ultimately results in rejection of the xenograft. There are several types of rejection organ xenografts are faced with, these include: Hyperac

36、ute rejection Acute vascular rejection Cellular rejection Chronic rejectionA rapid, violent hyperacute response results due to preformed natural antibodies, known as XNAs.9editHyperacute RejectionThis rapid and violent type of rejection occurs within minutes to hours from the time of the transplant.

37、 It is mediated by the binding of XNAs (xenoreactive natural antibodies) to the donor endothelium, causing activation of the human complement system which results in endothelial damage, inflammation, thrombosis and necrosis of the transplant. XNAs are first produced and begin circulating in the bloo

38、d in neonates, after colonization of the bowel by bacteria which have galactose moieties on their cell walls. Most of these antibodies are the IgM class, but also include IgG, and IgA. .8. The epitope XNAs target is an -linked galactose moiety, Gal-1,3Gal (also called the -Gal epitope), produced by

39、the enzyme -galactosyl transferase. 10. Most non-primates contain this enzyme thus, this epitope is present on the organ epithelium and is perceived as a foreign antigen by primates, which lack the galactosyl transferase enzyme. In pig to primate xenotransplantation, XNAs recognize porcine glycoprot

40、eins of the integrin family .8. The binding of XNAs initiate complement activation through the classical complement pathway. Complement activation causes a cascade of events leading to: destruction of endothelial cells, platlet degranulation, inflammation, coagulation, fibrin deposition, and hemorrh

41、age. The end result is thrombosis and necrosis of the xenograft .8.editOvercoming Hyperacute rejectionSince hyperacute rejection presents such a barrier to the success of xenografts several strategies to overcome it are under investigation:Interruption of the complement cascade The recipient's c

42、omplement cascade can be inhibited through the use of cobra venom factor (which depletes C3), soluble complement receptor type 1, anti-C5 antibodies, or C1 inhibitor (C1-INH). Disadvantages of this approach include the toxicity of cobra venom factor, and most importantly these treatments would depri

43、ve the individual of a functional complement system .7Transgeneic organs (Genetically engineered pigs)1,3 galactosyl transferase gene knockouts - These pigs dont contain the gene which codes for the enzyme responsible for expression of the immunogeneic gal-1,3Gal moiety (the -Gal epitope) 11.Increas

44、ed expression of H-transferase ( 1,2 fucosyltransferase), an enzyme that competes with galactosyl transferase. Experiments have shown this reduces -Gal expression by 70% 12.Expression of human complement regulators (CD55, CD46, and CD59) to inhibit the complement cascade 13.Plasmaphoresis, on humans

45、 to remove 1,3 galactosyltransferase, reduces the risk of activation of effector cells such as CTL (CD8 T cells), complement pathway activation and delayed type hypersensitivity (DTH).editAcute Vascular RejectionAlso known as delayed xenoactive rejection, this type of rejection occurs in discordant

46、xenografts within 2 to 3 days, if hyperacute rejection is prevented. The process is much more complex than hyperacute rejection and is currently not completely understood. Acute vascular rejection requires de novo protein synthesis and is driven by interactions between the graft endothelial cells an

47、d host antibodies, macrophages, and platelets. The response is characterized by an inflammatory infiltrate of mostly macrophages and natural killer cells (with small numbers of T cells), intravascular thrombosis, and fibrinoid necrosis of vessel walls 10. Binding of the previously mentioned XNAs to

48、the donor endothelium leads to the activation of host macrophages as well as the endothelium itself. The endothelium activation is considered type II since gene induction and protein synthesis are involved. The binding of XNAs ultimately leads to the development of a procoagulant state, the secretio

49、n of inflammatory cytokines and chemokines, as well as expression of leukocyte adhesion molecules such as E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) .8. This response is further perpetuated as normally binding between regulatory proteins an

50、d their ligands aid in the control of coagulation and inflammatory responses. However, due to molecular incompatibilities between the molecules of the donor species and recipient (such as porcine major histocompatibility complex molecules and human natural killer cells), this may not occur 10.editOv

51、ercoming Acute Vascular RejectionDue to its complexity, with the use of immunosuppresive drugs along with a wide array of approaches are necessary to prevent acute vascular rejection, and include: Administering a synthetic thrombin inhibitor to modulate thrombogenesis Depletion of anti-galactose ant

52、ibodies (XNAs) by techniques such as immunoadsorption, to prevent endothelial cell activation Inhibiting activation of macrophages (stimulated by CD4+ T cells) and NK cells (stimulated by the release of Il-2). Thus, the role of MHC molecules and T cell responses in activation would have to be reasse

53、ssed for each species combo 10.editAccommodationIf hyperacute and acute vascular rejection are avoided accommodation is possible, which is the survival of the xenograft despite the presence of circulating XNAs. The graft is given a break from humoral rejection 14 when the complement cascade is inter

54、rupted, circulating antibodies are removed, or their function is changed, or there is a change in the expression of surface antigens on the graft. This allows the xenograft to up-regulate and express protective genes, which aid in resistance to injury, such as heme oxygenase-1 (an enzyme that cataly

55、zes the degradation of heme) .8.editCellular rejectionRejection of the xenograft in hyperactute and acute vascular rejection is due to the response of the humoral immune system, since the response is elicited by the XNAs. Cellular rejection is based on cellular immunity, and is mediated by:1. Natura

56、l killer cells, which accumulate in and damage the xenograft; and2. T-lymphocytes - which are activated by MHC molecules through both direct and indirect xenorecognition.In direct xenorecognition, antigen presenting cells from the xenograft present peptides to recipient CD4+ T cells via xenogeneic M

57、HC class II molecules, resulting in the production of interleukin 2 (IL-2). Indirect xenorecognition involves the presentation of antigens from the xenograft by recipient antigen presenting cells to CD4+ T cells. Antigens of phagocytosed graft cells can also be presented by the hosts class I MHC mol

58、ecules to CD8+ T cells.715. The strength of cellular rejection in xenografts remains uncertain, however it is expected to be stronger than in allografts due to differences in peptides among different animals. This leads to more antigens potentially recognized as foreign, thus eliciting a greater ind

59、irect xenogenic response .7editOvercoming Cellular rejectionA proposed strategy to avoid cellular rejection is to induce donor non-responsiveness using haematopoietic chimerism. Donor stem cells are introduced into the bone marrow of the recipient, where they coexist with the recipients stem cells. The bone marrow stem cells give rise to cells of all haematopoietic lineages, through the pro