最新2013年4月11日《自然》雜志上一篇關(guān)于干細(xì)胞應(yīng)用方面的文章，報(bào)道了干細(xì)胞治療領(lǐng)域的一個(gè)真正實(shí)際應(yīng)用的領(lǐng)域：獸醫(yī)學(xué)。文章的題目是Stem cells boom in vetclinics。文章中提到，在人類干細(xì)胞謹(jǐn)慎應(yīng)用的同時(shí)，在馬、狗和貓，甚至老虎身上取得了非常令人激動(dòng)的效果。這應(yīng)該引起我們的關(guān)注和思考。關(guān)于干細(xì)胞，我們是否過于謹(jǐn)慎，對(duì)某些其他手段無能為力的疾病，在一定規(guī)范下，大膽使用干細(xì)胞是否應(yīng)該提倡和鼓勵(lì)。另外，對(duì)學(xué)者們也有提示作用，也許在人體研究存在困難的情況下，找找動(dòng)物兄弟幫助，甚至植物，也許可以獲得意想不到的收獲。干科學(xué)有時(shí)候也不能太死板。
在美國，病人試圖使用未經(jīng)證實(shí)的干細(xì)胞療法會(huì)受到政府的限制。但是來自弗吉尼亞的賽馬Vinty不需要理會(huì)美國政府的規(guī)定。毫無困難地獲得干細(xì)胞注射治療傷腿的肌腱。它獲得意想不到的治療效果，并得以重新回到訓(xùn)練場。
不過最新的FDA規(guī)定可能會(huì)限制干細(xì)胞在動(dòng)物醫(yī)學(xué)上的應(yīng)用，因?yàn)槔系囊?guī)定已經(jīng)使用了10年，面臨著更新。據(jù)說新的規(guī)定年底就會(huì)執(zhí)行，許多人開始擔(dān)心，這一新規(guī)定可能會(huì)導(dǎo)致動(dòng)物們無法嘗試這些沒有被證實(shí)的治療技術(shù)，甚至?xí)g接阻礙人類臨床醫(yī)學(xué)的發(fā)展。
由于沒有明確的限制性規(guī)定，這個(gè)行業(yè)已經(jīng)悄然興起。加利福尼亞一個(gè)獸醫(yī)干細(xì)胞公司專門提供干細(xì)胞治療各類動(dòng)物。自2004年，他們已經(jīng)給超過5000匹馬、4300只狗和120只貓等動(dòng)物患者們進(jìn)行了干細(xì)胞治療。更厲害的是肯塔基州尼古拉斯維爾的MediVet，他們自2010年以來給超過10000匹馬提供干細(xì)胞治療的服務(wù)。一些大學(xué)的獸醫(yī)系，獨(dú)自或經(jīng)過公司運(yùn)作，給無數(shù)動(dòng)物提供這種服務(wù)。
干細(xì)胞在馬、狗、貓用的比較多，也有人用于老虎甚至海豚，甚至考慮用干細(xì)胞治療各類肝臟疾病和糖尿病。
許多獸醫(yī)提供未經(jīng)證實(shí)的干細(xì)胞療法，以滿足客戶的要求，加州大學(xué)戴維斯分校的獸醫(yī)專業(yè)的Borjesson多麗說?！凹词箾]有證據(jù)支持，許多獸醫(yī)臨床醫(yī)生仍積極采用這種方法”。像人類尋求治療，大部分用于動(dòng)物治療的細(xì)胞是間充質(zhì)干細(xì)胞，這種干細(xì)胞具有可分化成多種細(xì)胞類型的能力，包括骨和軟骨，已證明間充質(zhì)干細(xì)胞具有很好的抗炎和其他效果。培養(yǎng)這種細(xì)胞的技術(shù)已經(jīng)非常成熟，技術(shù)人員只需要從脂肪或骨髓中提取間充質(zhì)，就可以培養(yǎng)出高濃度的能用于治療的間充質(zhì)干細(xì)胞。
FDA對(duì)使用人類骨髓間充質(zhì)干細(xì)胞的態(tài)度非常明確，干細(xì)胞屬于藥物，必須首先被證實(shí)安全有效才可以應(yīng)用。目前沒有任何MSC治療被批準(zhǔn)。雖然對(duì)獸醫(yī)的要求和人類臨床醫(yī)學(xué)不同，FDA雖然沒有打擊，但也確實(shí)沒有批準(zhǔn)任何一家獸醫(yī)干細(xì)胞療法。與此形成鮮明對(duì)比的是，FDA高調(diào)反對(duì)給人類提供未經(jīng)證實(shí)的人類干細(xì)胞治療。例如美國德克薩斯州Celltex Therapeutics ofSugar Land曾經(jīng)將msc用于人類患者，2012年9月因FDA的介入而被中斷。
更準(zhǔn)確全面的信息，請(qǐng)看以下《自然》上的原文：
Horses, dogs and even a tiger have received the unproven therapies. Now,drug regulators plan to weigh in.
David Cyranoski
10April 2013
Patients seeking unproven stem-cell therapies in the United States oftenrun up against government restrictions. But Vintage ‘Vinty’ Mark ofLovettsville, Virginia, had no difficulty getting such injections to treat aninjured tendon in his leg. The leg improved dramatically, and Vinty went backto training — to be a racehorse.
New guidance from the US Food and Drug Administration (FDA) could,however, soon rein in veterinary uses of stem cells, a practice that hasexploded in the United States over the past decade, even though most therapiesare unproven. Many researchers and veterinarians say that the guidance, a draftof which the agency plans to issue by the end of the year, is overdue. Butothers worry that FDA interference could hamper research that could benefitanimals — and their human companions.
In the absence of clear regulations, the industry has burgeoned. Vet-Stem,a company based in Poway, California, has provided stem-cell treatments to morethan 5,000 horses, 4,300 dogs and 120 cats since treating its first patient in2004. Kits provided by MediVet America, based in Nicholasville, Kentucky, havebeen used to produce stem-cell injections for more than 10,000 horses since2010. University veterinary departments, independently or through spin-offcompanies, have offered such services to thousands more animals. Veterinarianssend patients’ tissue samples to the centres to have cells extracted or,increasingly, turn to kits that allow them to extract the cells in-house.
Stem cells are most often used to treat horses, dogs and cats, butclinicians have also sought to use them to repair a lumbar fracture in a Bengaltiger and arthritis in pigs. Researchers have also found stem cells in the fatof bottle-nose dolphins, raising hopes for treating the marine-mammal versionsof liver disease and type 2 diabetes. “There’s not a large vet practice that’snot using them,” says Wesley Sutter, a veterinarian at Lexington Equine Surgeryand Sports Medicine in Kentucky. “Some claim [the treatment] cures everything.”
Many veterinarians offer unproven stem-cell therapies to satisfy demandingcustomers, says Dori Borjesson, who specializes in veterinary medicine at theUniversity of California, Davis. “Clinicians are sucked into giving treatment”even when there’s not research to back up uses, she says.
Like the treatments sought by humans, most of those used in animalsinvolve mesenchymal stem cells (MSCs), which can mature into a wide variety ofcell types, including bone and cartilage, and have been shown to haveanti-inflammatory and other beneficial effects. MSCs are extracted from fat orbone marrow and can be cultured or prepared for injection in concentrated form.
The FDA’s position on the use of MSCs in humans is clear. It says that thecells are drugs and therefore must be proved safe and effective before they canbe used in treatment, except under certain conditions. No MSC treatments havebeen approved. But the FDA has different regulations for veterinary medicine,and these do not clearly address MSCs. The agency has not approved anyveterinary stem-cell therapies, but neither has it cracked down on any. This isin stark contrast to its high-profile actions against purveyors of unprovenhuman stem-cell treatments, such as Celltex Therapeutics of Sugar Land,Texas,which treated patients with MSCs until the FDA stepped in last September.
That doesn’t mean that the agency is not concerned, says Lynne Boxer, aveterinary medical officer in the FDA’s Office of New Animal Drug Evaluation inRockville, Maryland. “As with any type of drug product, there are risks andbenefits,” she says. “With stem cells, there is the potential for diseasetransmission and tumour formation.” She declines, however, to say whethercurrent practices are against FDA rules, or to elaborate on what the new draftguidance is likely to contain.
The guidance void is irksome, says Karl Nobert, a lawyer at Squire Sandersin Washington DC, who has represented companies seeking direction from the FDA.His concern is not just professional: he is Vinty’s former owner, and says thathe saw “incredible improvement” as the horse healed, with normal tendon fibresrather than scar tissue at the injury site.
Research backs up the benefits of stem-cell treatments in someapplications. A 2007 double-blind study in 21 dogs showed that MSCs improvedchronic osteoarthritis1.A 2010 report showed that injections of tissue rich in MSCs helped damaged legbones to heal in 12 horses2.And a 2012 study, much discussed by veterinarians, showed that MSCs from bonemarrow helped racehorses with tendon injuries avoid re-injury3.
Researchers recognize that many studies of veterinary stem-cell treatmentshave a major weakness: they lack control groups or blinded evaluation, whichare crucial to show whether the treatments truly make a difference. “It isexceptionally difficult to do blinded studies in our patients because theowners or trainers specifically seek an institution for stem-cell therapy,”says Lisa Fortier, a veterinary surgeon at Cornell University in Ithaca, NewYork, and a co-author of the 2010 cartilage study.
Without controlled trials, comparisons between treated and untreatedanimals are difficult. Owners who have paid a few thousand dollars for atherapy are more likely to follow strict rehabilitation protocols than thosewho have not. They are also more likely to rush horses back into action, whichwould skew reported recovery time, a measure of a treatment’s effectiveness.And placebo effects — on the owners — can be powerful. “The cat looks like hellto me but the owner says: ‘She looks so great. I love stem cells’,” saysBorjesson.
Many veterinarians think that studying stem-cell therapies in largeanimals, which are more physiologically similar to humans than the mice oftenused in preclinical research, could be a powerful model for medicine — ifstudies are done right. Borjesson is running studies (with “as much blinding aspossible”) of stem-cell treatments for dry eye, another eye condition calledrecurrent uveitis, and inflammatory bowel disease in clients’ pet dogs. She isalso collaborating with researchers in human regenerative medicine, so that herfindings can inform their studies of experimental therapies. And David Frisbie,a veterinary surgeon at Colorado State University in Fort Collins, is workingwith doctors to apply lessons from animal stem-cell treatments to jointinjuries in humans.
If the pending FDA guidance clearly designates animal stem cells as drugs,veterinarians and companies who want to deploy such treatments will first haveto conduct clinical trials, which Frisbie estimates could cost at least US$5million each. Nobert, meanwhile, is optimistic that veterinary stem-cellcompanies and university researchers will find ways to “design creativeregulatory approval strategies to streamline and expedite thereview-and-approval process” — which might, in turn, influence the humanstem-cell regulatory process.
Still, he worries that overly stringent FDA rules about, for example, howcells are characterized, could “make the ultimate commercial priceunreasonable”.
For Vinty, it’s a moot point. He’s had his stem cells. But even with histendon fixed, he was too slow to race. He now gives riding lessons to children.
Nature496, 148–149 (11 April 2013) doi:10.1038/496148a
1. Black, L. L. et al.Vet. Ther.8, 272–284 (2007).
2. Show context
3. Fortier, L. A. et al.J. Bone Joint. Surg. Am.18, 1927–1937 (2010).
4. Show context
Godwin, E. E., Young, N. J., Dudhia, J.,Beamish, I. C. & Smith, R. K. W. Equine Vet. J.44, 25–32(2012).
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