Fahy Gregory M, Wowk Brian, Wu Jun
21st Century Medicine, Inc., Rancho Cucamonga, California 91730, USA.
Rejuvenation Res. 2006 Summer;9(2):279-91. doi: 10.1089/rej.2006.9.279.
Transplantation can be regarded as one form of "antiaging medicine" that is widely accepted as being effective in extending human life. The current number of organ transplants in the United States is on the order of 20,000 per year, but the need may be closer to 900,000 per year. Cadaveric and living-related donor sources are unlikely to be able to provide all of the transplants required, but the gap between supply and demand can be eliminated in principle by the field of regenerative medicine, including the present field of tissue engineering through which cell, tissue, and even organ replacements are being created in the laboratory. If so, it could allow over 30% of all deaths in the United States to be substantially postponed, raising the probability of living to the age of 80 by a factor of two and the odds of living to 90 by more than a factor of 10. This promise, however, depends on the ability to physically distribute the products of regenerative medicine to patients in need and to produce these products in a way that allows for adequate inventory control and quality assurance. For this purpose, the ability to cryogenically preserve (cryopreserve) cells, tissues, and even whole laboratory-produced organs may be indispensable. Until recently, the cryopreservation of organs has seemed a remote prospect to most observers, but developments over the past few years are rapidly changing the scientific basis for preserving even the most difficult and delicate organs for unlimited periods of time. Animal intestines and ovaries have been frozen, thawed, and shown to function after transplantation, but the preservation of vital organs will most likely require vitrification. With vitrification, all ice formation is prevented and the organ is preserved in the glassy state below the glass transition temperature (T(G)). Vitrification has been successful for many tissues such as veins, arteries, cartilage, and heart valves, and success has even been claimed for whole ovaries. For vital organs, a significant recent milestone for vitrification has been the ability to routinely recover rabbit kidneys after cooling to a mean intrarenal temperature of about -45 degrees C, as verified by life support function after transplantation. This temperature is not low enough for long-term banking, but research continues on preservation below -45 degrees C, and some encouraging preliminary evidence has been obtained indicating that kidneys can support life after vitrification. Full development of tissue engineering and organ generation from stem cells, when combined with the ability to bank these laboratory-produced products, in theory could dramatically increase median life expectancy even in the absence of any improvements in mitigating aging processes on a fundamental level.
移植可被视为“抗衰老医学”的一种形式，这种医学被广泛认为在延长人类寿命方面是有效的。目前美国每年的器官移植数量约为2万例，但需求可能接近每年90万例。尸体供体和亲属活体供体来源不太可能提供所需的所有移植器官，但再生医学领域原则上可以消除供需差距，包括当前的组织工程领域，通过该领域可以在实验室中制造细胞、组织甚至器官替代品。如果是这样，它可以使美国超过30%的死亡人数大幅推迟，将活到80岁的概率提高一倍，活到90岁的几率提高10倍以上。然而，这一前景取决于能否将再生医学产品实际分发给有需要的患者，并以允许进行充分库存控制和质量保证的方式生产这些产品。为此，低温保存（冷冻保存）细胞、组织甚至整个实验室制造的器官的能力可能是必不可少的。直到最近，对大多数观察者来说，器官的冷冻保存似乎还是一个遥远的前景，但过去几年的进展正在迅速改变即使是最难保存和最脆弱的器官进行无限期保存的科学基础。动物的肠道和卵巢已经被冷冻、解冻，并在移植后显示出功能，但重要器官的保存很可能需要玻璃化。通过玻璃化，可防止所有冰晶形成，器官在低于玻璃化转变温度（T(G)）的玻璃态下保存。玻璃化在许多组织如静脉、动脉、软骨和心脏瓣膜上已经取得成功，甚至有人声称整个卵巢也取得了成功。对于重要器官，玻璃化最近的一个重要里程碑是，将兔肾冷却至平均肾内温度约-45摄氏度后，能够常规恢复其功能，移植后的生命支持功能证明了这一点。这个温度对于长期保存来说还不够低，但关于低于-45摄氏度保存的研究仍在继续，并且已经获得了一些令人鼓舞的初步证据，表明肾脏在玻璃化后能够维持生命。组织工程和从干细胞生成器官的全面发展，再加上储存这些实验室制造产品的能力，理论上即使在基本层面上减缓衰老过程没有任何改善的情况下，也能显著提高平均预期寿命。
