The effective bioengineering method of implantation decellularized renal extracellular matrix scaffolds.

Yong Guan,Xiaoshuai Xie,Feng Kong,Jue Wang,Denglu Zhang,Kailin Li,Guanghui Cheng,Chao Sun,Yun Luan,Shuangde Liu,Yuqiang Liu,Shengtian Zhao

doi:10.18632/oncotarget.5304

Yong Guan, Xiaoshuai Xie + Show 10 more

Open Access

https://doi.org/10.18632/oncotarget.5304

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Abstract

End stage renal disease (ESRD) is a progressive loss of kidney function with a high rate of morbidity and mortality. Transplantable organs are hard to come by and hold a high risk of recipient immune rejection. We intended to establish a more effective and faster method to decellularize and recellularize the kidney scaffold for transplant and regeneration. We successfully produced renal scaffolds by decellularizing rat kidneys with 0.5% sodium dodecyl sulfate (SDS), while still preserving the extracellular matrix (ECM) 3D architecture, an intact vascular tree and biochemical components. We recellularized the kidney scaffolds with mouse embryonic stem (ES) cells that then populated and proliferated within the glomerular, vascular, and tubular structures. After in vivo implantation, these recellularized scaffolds were easily reperfused, tolerated blood pressure and produced urine with no blood leakage. Our methods can successfully decellularize and recellularize rat kidneys to produce functional renal ECM scaffolds. These scaffolds maintain their basic components, retain intact vasculature and show promise for kidney regeneration.

Highlights

Chronic kidney disease is a major cause of mortality and morbidity worldwide, affecting about 8% to 16% of the global adult population [1]
Electron microscopy indicated that no nuclear structure was found, the integrity of the extracellular matrix (ECM) was not disrupted in the acellular kidney scaffolds as shown by the presence of a continuous membrane of the Bowman’s capsule, the basement membrane of the glomerular capillaries and mesangial matrix (Fig. 1E & 1F)
We demonstrated that the rat kidneys had been completely decellularized, some cytokines still remained within the scaffolds in concentrations that might be sufficient to contribute to renal regeneration after recellularization

Summary

Introduction

Chronic kidney disease is a major cause of mortality and morbidity worldwide, affecting about 8% to 16% of the global adult population [1]. Recent advances in tissue engineering and regenerative medicine have shown promise for producing whole organs for transplantation This concept involves the use of naturally occurring extracellular matrix (ECM) and stem cells or some adult cells. Functional cells are seeded on and/or within a natural scaffold, which could be referred to as recellularization Researchers have applied this tissue engineering technology to produce functional substitutes for some organs, such as blood vessel [9,10,11,12,13], bladder [14], heart [15, 16], liver [17,18,19], intestine [20, 21], muscle [22], trachea [23,24,25], lung [26,27,28], and urethra [29]

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