Engineering a microcirculation for perfusion control of ex vivo–assembled organ systems: Challenges and opportunities

Kottamasu, Pavan; Herman, Ira M.

doi:10.1177/2041731418772949

Cited by 8 publications

(5 citation statements)

References 129 publications

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“…In addition to treating diseased organs during EVMP with subsequent reimplantation, bioengineering is furthermore envisioned to enable the recreation of tissue parts for subsequent implantation as an alternative strategy to organ transplantation. Therefore, EVMP has been proposed as an interface for the decellularization and the recellularization of bioartificial organs under physiological conditions with subsequent implantation ( 175 , 176 ). In general, decellularization was achieved in a broad range of organs during EVMP with preserved organ architecture and ECM components in addition to low levels of DNA and physiological abundance of glycosaminoglycans and chemical and mechanical components of the ECMs ( 177 ).…”

Section: Potential Of Evmp Beyond Ordinary Graft Preservationmentioning

confidence: 99%

Pushing the boundaries of innovation: the potential of ex vivo organ perfusion from an interdisciplinary point of view

Iske,

Schroeter,

Knoedler

et al. 2023

Front. Cardiovasc. Med.

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Ex vivo machine perfusion (EVMP) is an emerging technique for preserving explanted solid organs with primary application in allogeneic organ transplantation. EVMP has been established as an alternative to the standard of care static-cold preservation, allowing for prolonged preservation and real-time monitoring of organ quality while reducing/preventing ischemia–reperfusion injury. Moreover, it has paved the way to involve expanded criteria donors, e.g., after circulatory death, thus expanding the donor organ pool. Ongoing improvements in EVMP protocols, especially expanding the duration of preservation, paved the way for its broader application, in particular for reconditioning and modification of diseased organs and tumor and infection therapies and regenerative approaches. Moreover, implementing EVMP for in vivo-like preclinical studies improving disease modeling raises significant interest, while providing an ideal interface for bioengineering and genetic manipulation. These approaches can be applied not only in an allogeneic and xenogeneic transplant setting but also in an autologous setting, where patients can be on temporary organ support while the diseased organs are treated ex vivo, followed by reimplantation of the cured organ. This review provides a comprehensive overview of the differences and similarities in abdominal (kidney and liver) and thoracic (lung and heart) EVMP, focusing on the organ-specific components and preservation techniques, specifically on the composition of perfusion solutions and their supplements and perfusion temperatures and flow conditions. Novel treatment opportunities beyond organ transplantation and limitations of abdominal and thoracic EVMP are delineated to identify complementary interdisciplinary approaches for the application and development of this technique.

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Section: Potential Of Evmp Beyond Ordinary Graft Preservationmentioning

confidence: 99%

Pushing the boundaries of innovation: the potential of ex vivo organ perfusion from an interdisciplinary point of view

Iske,

Schroeter,

Knoedler

et al. 2023

Front. Cardiovasc. Med.

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show abstract

“…However, recreating the blood vessel in a laboratory for whole artificial organ development is an uphill task that the scientific community started over a decade ago. In engineering, any tissue destined for transplantation must have well-developed blood vessels which vary in size and composition, among other regulating factors of vascularization (Cao et al, 2007;Kottamasu and Herman, 2018).…”

Section: Controlling the Spatiotemporal Development Of Micro-vessels ...mentioning

confidence: 99%

“…Many strategies have been used as growth factors and for controlling the mechanical properties, including extracellular matrix components such as glycosaminoglycan at a tissue-level redevelopment. Such strategies need to be recapitulated at the whole-organ level (Kottamasu and Herman, 2018). Very few reports exist where the authors have used growth factor loading to prove vessel development at both capillary and larger-vessel levels.…”

Section: Controlling the Spatiotemporal Development Of Micro-vessels ...mentioning

confidence: 99%

Vascular reconstruction of the decellularized biomatrix for whole-organ engineering—a critical perspective and future strategies

Gupta,

Sharma,

Petrovski

et al. 2023

Front. Bioeng. Biotechnol.

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Whole-organ re-engineering is the most challenging goal yet to be achieved in tissue engineering and regenerative medicine. One essential factor in any transplantable and functional tissue engineering is fabricating a perfusable vascular network with macro- and micro-sized blood vessels. Whole-organ development has become more practical with the use of the decellularized organ biomatrix (DOB) as it provides a native biochemical and structural framework for a particular organ. However, reconstructing vasculature and re-endothelialization in the DOB is a highly challenging task and has not been achieved for constructing a clinically transplantable vascularized organ with an efficient perfusable capability. Here, we critically and articulately emphasized factors that have been studied for the vascular reconstruction in the DOB. Furthermore, we highlighted the factors used for vasculature development studies in general and their application in whole-organ vascular reconstruction. We also analyzed in detail the strategies explored so far for vascular reconstruction and angiogenesis in the DOB for functional and perfusable vasculature development. Finally, we discussed some of the crucial factors that have been largely ignored in the vascular reconstruction of the DOB and the future directions that should be addressed systematically.

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“… 115 , 116 One strategy is to implant hepatocyte aggregates near the existing blood vessels in vivo to promote angiogenesis. 117 As an example, Yap et al 9 implanted murine liver progenitor cells embedded in growth factor-reduced Matrigel into the vascularized chamber fitted around the superficial epigastric vascular pedicle at the groin of SCID mice. After 14 days, glandular organization of cells and vascularization were only seen in the chambers with implantation of cell aggregates but not single-cell suspensions.…”

Section: Bioengineering Of Functional Hepatic Constructsmentioning

confidence: 99%

Stem cell therapy and tissue engineering strategies using cell aggregates and decellularized scaffolds for the rescue of liver failure

et al. 2021

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Liver failure is a lethal condition with hepatocellular dysfunction, and liver transplantation is presently the only effective treatment. However, due to the limited availability of donors and the potential immune rejection, novel therapeutic strategies are actively sought to restore the normal hepatic architectures and functions, especially for livers with inherited metabolic dysfunctions or chronic diseases. Although the conventional cell therapy has shown promising results, the direct infusion of hepatocytes is hampered by limited hepatocyte sources, poor cell viability, and engraftment. Hence, this review mainly highlights the role of stem cells and progenitors as the alternative cell source and summarizes the potential approaches based on tissue engineering to improve the delivery efficiency of cells. Particularly, the underlying mechanisms for cell therapy using stem cells and progenitors are discussed in two main aspects: paracrine effect and cell differentiation. Moreover, tissue-engineering approaches using cell aggregates and decellularized liver scaffolds for bioengineering of functional hepatic constructs are discussed and compared in terms of the potential to replicate liver physiological structures. In the end, a potentially effective strategy combining the premium advantages of stem cell aggregates and decellularized liver scaffolds is proposed as the future direction of liver tissue engineering and regeneration.

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Engineering a microcirculation for perfusion control of ex vivo–assembled organ systems: Challenges and opportunities

Cited by 8 publications

References 129 publications

Pushing the boundaries of innovation: the potential of ex vivo organ perfusion from an interdisciplinary point of view

Pushing the boundaries of innovation: the potential of ex vivo organ perfusion from an interdisciplinary point of view

Vascular reconstruction of the decellularized biomatrix for whole-organ engineering—a critical perspective and future strategies

Stem cell therapy and tissue engineering strategies using cell aggregates and decellularized scaffolds for the rescue of liver failure

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