哥伦比亚大学建立了一个组织工程技术平台，给心脏打补丁后可以使心脏组织自我修复，该这项令人激动的研究成果将发布在 National Academy of Sciences。# r# D2 q4 s4 I2 x4 M Engineers Patch a Heart: Tissue-Engineering Platform Enables Heart Tissue to Repair Itself* j- ^: s9 }8 Y. |& G& \
' F/ c4 ^& _) k( hScienceDaily (May 7, 2011) — Researchers at Columbia Engineering have established a new method to patch a damaged heart using a tissue-engineering platform that enables heart tissue to repair itself. This breakthrough, recently published in the Proceedings of the National Academy of Sciences, is an important step forward in combating cardiovascular disease, one of the most serious health problems of our day. ' n4 k5 P2 f6 m; w: L6 v--------------------------------------------------------------------------------! ~5 N! x8 W6 w# k0 ^: V) a, E
. X+ n H$ g5 M8 z ~Led by Gordana Vunjak-Novakovic, Professor of Biomedical Engineering at Columbia University's Fu Foundation School of Engineering and Applied Science, the researchers developed a novel cell therapy to treat myocardial infarction (heart damage that follows a heart attack). They were able, for the first time, to combine the use of human repair cells that were conditioned during in-vitro culture to maximize their ability to revascularize and improve blood flow to the infarcted tissue with a fully biological composite scaffold designed to deliver these cells to the damaged heart. With this platform, they could both keep the cells within the infarct bed (in contrast to the massive cell loss associated with infusion of cells alone) and enhance cell survival and function in the infarct bed, where most of the cells would have died because of the obstruction of their blood supply. ! g. a( W& W4 {* { + T6 h& ^+ c/ U3 {"We are very excited about this new technique," said Dr. Vunjak-Novakovic. "This platform is very adaptable and we believe it could be readily extended to the delivery of other types of human stem cells we are interested in to rebuild the heart muscle and further our research of the mechanisms underlying heart repair." 0 t0 c- s, H& I6 s/ ^7 V u, A# u1 G, m% Y) B( l- SIn effect, the Columbia Engineering team (with Amandine Godier-Fournemont and Timothy Martens as lead authors) removed the cells of a human heart muscle -- the myocardium -- leaving a protein scaffold with intact architecture and mechanical properties. They filled the scaffold with human mesenchymal progenitors (stem cells that can differentiate into many cell types) and then applied the patches to damaged heart tissue. The patches promoted the growth of new blood vessels and released proteins that stimulated the native tissue to repair itself. Moreover, the team also used this controllable platform to identify the signaling mechanisms involved in the repair process, and expand our knowledge about the role of cells and scaffold design on heart repair. , Y0 @) z5 Q: M, Y9 Q: C 9 z0 u: L6 t: L N- B! `"It really is encouraging to make progress with 'instructing' cells to form human tissues by providing them with the right environments," noted Dr. Vunjak-Novakovic. "The cells are the real 'tissue engineers' -- we only design the environments so they can do their work. Because these environments need to mimic the native developmental milieu, the progress in the field is really driven by the interdisciplinary work of bioengineers, stem cell biologists, and clinicians. By enabling regeneration and replacement of our damaged tissues, we can help people live longer and better." ) p# x O' e5 E% Q% u' y" J; k5 J+ _1 @ p6 }5 ~: R
Dr. Vunjak-Novakovic and her team already have several active research projects that continue this line of work. They are now investigating the formation of a contractile cardiac patch using human stem cells that can give rise to both the muscle and vascular compartments of the heart muscle. They are also studying how the cells within such a cardiac patch, when implanted on infarcted heart tissue, develop their ability to generate mechanical force and electrical conduction, and how these functions can be modulated by in-vitro culture. ( o1 L: y: ~' H6 p( K9 U0 V7 m/ ]7 L# t: J7 x* [1 O5 S
"Ultimately, we envision this system as a possible point of care approach," said Dr. Vunjak-Novakovic, "with components actually produced and assembled in the operating room to most effectively target-signaling mechanisms involved in the repair process of someone's damaged heart." 0 g. q( j' q6 A! Y3 K / R5 h, [# _8 u; y/ J1 `0 K0 ]) [( XThe Columbia Engineering study has been supported by the NIH (National Institutes of Health).8 V: Y+ k# U: p9 h _
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Story Source: W/ u' {3 |8 m! o A$ c6 S7 a ) p$ _) p! J& z K8 X5 d- mThe above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Columbia University. 3 V9 X8 n/ m) [" J; X0 L! a0 o% Q3 M! z' p
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Journal Reference:" ]9 q0 {& E B
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A. F. G. Godier-Furnemont, T. P. Martens, M. S. Koeckert, L. Wan, J. Parks, K. Arai, G. Zhang, B. Hudson, S. Homma, G. Vunjak-Novakovic. Composite scaffold provides a cell delivery platform for cardiovascular repair. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1104619108 9 @/ k/ Z+ K% o' V# O" m5 G 作者: tpwang 时间: 2011-5-10 17:28
回复 sunsong7 的帖子 / H2 Y; y$ K6 \& o) o' A# d% T2 Z : q' K# N+ h% c4 ~原文及补充材料 K3 n1 J/ b# z6 a% x$ `( e, { ; c( ]8 B. d1 Z. Q5 Y# _$ }# k[attach]26707[/attach]* ^) r& H B# V- ]: l
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: w9 _0 Y3 D7 S5 [$ O( k+ |. E9 j6 o这个方法要从心脏移植手术的患者心脏上取组织，然后去细胞留下“支架”，再种上干细胞。大概其“效果”很大程度上得益于这个“天然”结构与心脏本身的“亲和度”？不过，这个程序是否有临床实用上的局限性，比如创伤性、时效性、技术操作难度，来源局限（自体）等。也可能为将来完全人工仿制支架提供一个模型。该研究一个重要的临床指标是所移植细胞旁分泌作用指导下的血管再生以及心电图检测的左心室功能改善，血管再生在心肌梗死病因和治疗上都是关键。但单纯血管再生能否及如何逆转缺血导致的心肌组织坏死，在这个模型下仍有待观察，需要有这个方法的长期动物模型。 . X/ T) @( w8 O7 ?6 o" q$ L& D6 ?9 t( U; Z* z; E6 f: ]( u; P
“打补丁”的比喻来源是衣物上有了窟窿，用补丁盖上。心肌缺血性坏死只是留下功能性“窟窿”，坏死结构还在那里呆着，这个坏死结构足够大的话会导致整个心脏心电环路功能紊乱，因为坏死的心肌不导电。所以，在坏死组织之上“打补丁”还是个非常“初级”的手段。终极的心脏坏死组织“再生”，即恢复心肌三维结构包括完整血管系统再生并与周围心脏组织再整合，其心电功能也要再恢复与整合，要想做到这一点，原坏死组织哪里去，是被“消纳”了，还是真的“再复苏”了（不大可能），还是被叠加的结构替代控制了，恐怕绕不过去。比如，该研究发现梗死组织（infarct be) 有血管再生（revascularization），这是否意味着坏死组织可以复活或有其他“变废为宝”过程，不得而知，作者由此直接跳到心脏功能保留（function preservation）上去了。, Q* |! K1 V) l; A( q$ P) V
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上述研究的“突破”，主要是概念性地表明ＴＧＦ－ｂ处理过的细胞加原生心肌支架的结合是一个比较有效的细胞engraftment手段，这个有效性得到了一些初步指标的证实。作者认为下一步可能是将细胞种类扩展到iPSC以及其他成体干细胞上。其实，上述机制问题更关键，想象一下要获得临床试验的准入，不可能没有上述关键指标的数据。临床还要一些年，如一位参与者所言。) q, D& c* E/ ~% M H. e