Kim Ick-Hee, Ko In Kap, Atala Anthony, Yoo James J
aWake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA bKonkuk University Medical College, Seoul, Korea.
Curr Opin Organ Transplant. 2015 Apr;20(2):165-70. doi: 10.1097/MOT.0000000000000173.
Renal transplantation is currently the only definitive treatment for end-stage renal disease; however, this treatment is severely limited by the shortage of implantable kidneys. To address this shortcoming, development of an engineered, transplantable kidney has been proposed. Although current advances in engineering kidneys based on decellularization and recellularization techniques have offered great promises for the generation of functional kidney constructs, most studies have been conducted using rodent kidney constructs and short-term in-vivo evaluation. Toward clinical translations of this technique, several limitations need to be addressed.
Human-sized renal scaffolds are desirable for clinical application, and the fabrication is currently feasible using native porcine and discarded human kidneys. Current progress in stem cell biology and cell culture methods have demonstrated feasibility of the use of embryonic stem cells, induced pluripotent stem cells, and primary renal cells as clinically relevant cell sources for the recellularization of renal scaffolds. Finally, approaches to long-term implantation of engineered kidneys are under investigation using antithrombogenic strategies such as functional reendothelialization of acellular kidney matrices.
In the field of bioengineering, whole kidneys have taken a number of important initial steps toward clinical translations, but many challenges must be addressed to achieve a successful treatment for the patient with end-stage renal disease.
肾移植是目前终末期肾病的唯一确定性治疗方法;然而,这种治疗方法受到可植入肾脏短缺的严重限制。为了解决这一缺点,人们提出了开发一种可移植的工程化肾脏。尽管目前基于去细胞化和再细胞化技术的肾脏工程进展为生成功能性肾脏构建体带来了巨大希望,但大多数研究都是使用啮齿动物肾脏构建体并进行短期体内评估。为了将该技术转化为临床应用,需要解决几个限制因素。
临床应用需要人尺寸的肾脏支架,目前使用天然猪肾和废弃人肾进行制造是可行的。干细胞生物学和细胞培养方法的当前进展已证明使用胚胎干细胞、诱导多能干细胞和原代肾细胞作为肾脏支架再细胞化的临床相关细胞来源是可行的。最后,正在研究使用抗血栓形成策略(如无细胞肾基质的功能性再内皮化)来长期植入工程化肾脏的方法。
在生物工程领域,全肾在向临床转化方面已经迈出了一些重要的初步步骤,但要成功治疗终末期肾病患者,还必须应对许多挑战。