Towards the development of a bioengineered uterus: Comparison of different protocols for rat uterus decellularization

Hellström, Mats; El-Akouri, Randa Racho; Sihlbom, Carina; Olsson, Bob; Lengqvist, Johan; Bäckdahl, Henrik; Johansson, Bengt R.; Olausson, Michael; Sumitran–Holgersson, Suchitra; Brännström, Mats

doi:10.1016/j.actbio.2014.08.018

Cited by 98 publications

(97 citation statements)

References 53 publications

(74 reference statements)

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“…For these reasons, and in line with what was developed for other whole organs,73,74,77,92,100 we and one other group evaluated different strategies to decellularize whole rat uterus. The rat uterus was isolated with an intact vascular tree (from the aorta to vena cava) from a donor rat so that a whole uterus scaffold could be obtained by decellularization, which then enable recellularization and transplantation with vascular anastomoses 41,68. Miyazaki and Maruyama used an SDS-based decellularization protocol originally optimized for the rat liver 100.…”

Section: Uterine Tissue Engineeringmentioning

confidence: 99%

“…Miyazaki and Maruyama used an SDS-based decellularization protocol originally optimized for the rat liver 100. At the same time, we developed three different decellularization protocols; two protocols were based on a combination of Triton-X100 and dimethyl sulfoxide (DMSO), where one protocol was buffered in phosphate buffered saline (PBS) for the duration of the procedure, while the other was non-buffered (de-ionized H 2 O) 41. Our third protocol was based on an ionic detergent called sodium deoxycholate (SDC) 41.…”

Section: Uterine Tissue Engineeringmentioning

confidence: 99%

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Uterine Tissue Engineering and the Future of Uterus Transplantation

2016

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The recent successful births following live donor uterus transplantation are proof-of-concept that absolute uterine factor infertility is a treatable condition which affects several hundred thousand infertile women world-wide due to a dysfunctional uterus. This strategy also provides an alternative to gestational surrogate motherhood which is not practiced in most countries due to ethical, religious or legal reasons. The live donor surgery involved in uterus transplantation takes more than 10 h and is then followed by years of immunosuppressive medication to prevent uterine rejection. Immunosuppression is associated with significant adverse side effects, including nephrotoxicity, increased risk of serious infections, and diabetes. Thus, the development of alternative approaches to treat absolute uterine factor infertility would be desirable. This review discusses tissue engineering principles in general, but also details strategies on how to create a bioengineered uterus that could be used for transplantation, without risky donor surgery and any need for immunosuppression. We discuss scaffolds derived from decellularized organs/tissues which may be recellularized using various types of autologous somatic/stem cells, in particular for uterine tissue engineering. It further highlights the hurdles that lay ahead in developing an alternative to an allogeneic source for uterus transplantation.

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Section: Uterine Tissue Engineeringmentioning

confidence: 99%

Section: Uterine Tissue Engineeringmentioning

confidence: 99%

Uterine Tissue Engineering and the Future of Uterus Transplantation

2016

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“…There existed signs of a preserved vascular bed, since perfusion with red dye showed flow from the large vessels to the capillaries of the uterine scaffold. In our initial study we compared three different decellularization protocols [57]. Two protocols were based on a combination of Triton-X100 and dimethyl sulfoxide (DMSO), where one protocol was buffered by phosphate buffered saline (PBS) for the duration of the procedure, while the other utilized non-buffered deionized H 2 O.…”

Section: Introductionmentioning

confidence: 99%

Uterus transplantation and beyond

Brännström

2017

J Mater Sci: Mater Med

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Uterus transplantation is today the only available treatment for absolute uterine factor infertility which is caused by either congenital/surgical uterine absence or that a present uterus is non-functioning. Structured animal-based research, from rodents to nonhuman primates, was the scientific basis for a successful introduction of uterus transplantation as a clinical procedure. The patient groups for uterus transplantation, the preclinical research and data from the published human cases will be covered herein. During recent years the concept of bioengineering of organs and tissues has emerged. Creation of a bioengineered uterus is in the initial research state, with experiments performed in rodents. The research that has been performed to create a bioengineered uterus will be summarized. In conclusion, uterus transplantation is now a clinical experimental procedure for treatment of uterine factor infertility. In parallel to the establishment of this combined assisted reproduction technique and transplantation procedure as a routine clinical procedure, we predict that uterus bioengineering will develop further towards introduction within the human setting, but that this process will take several years.

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“…The first group received 0.1 nM E2 (day 0-7), 1 nM E2 (day 7-21), and 0.1 nM E2 (day 21-28). The second group received 0.1 nM E2 (day 0-7), 1 nM E2 (day 7-14), 1 nM E2 + 10 nM P4 (day 14-21), and 0.1 nM E2 + 50 nM P4 (day [21][22][23][24][25][26][27][28]. The third group received 0.1 nM E2 (day 0-7), 1 nM E2 (day 7-14), 1 nM E2 + 10 nM P4 + 0.5 mM dibutyryl cyclic Adenosine monophosphate (AMP) (dbcAMP) (day 14-21), and 0.1n M E2 + 50 nM P4 + 0.5 mM dbcAMP (day 21-28).…”

Section: Twenty-eight-day Hormone Protocolmentioning

confidence: 99%

“…Several decellularization and recellularization techniques have been established in tissue engineering [18][19][20][21]. Different techniques have been comparatively used to decellularize murine uterus [22,23]. Recently, successful decellularization, recellularization, and transplantation of uterine patches which led to successful pregnancies were shown in rats [24,25].…”

Section: Introductionmentioning

confidence: 99%

Development of a novel human recellularized endometrium that responds to a 28-day hormone treatment†

Olalekan

Burdette

Getsios

et al. 2017

Biology of Reproduction

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Three-dimensional (3D) in vitro models have been established to study the physiology and pathophysiology of the endometrium. With emerging evidence that the native extracellular matrix (ECM) provides appropriate cues and growth factors essential for tissue homeostasis, we describe, a novel 3D endometrium in vitro model developed from decellularized human endometrial tissue repopulated with primary endometrial cells. Analysis of the decellularized endometrium using mass spectrometry revealed an enrichment of cell adhesion molecules, cytoskeletal proteins, and ECM proteins such as collagen IV and laminin. Primary endometrial cells within the recellularized scaffolds proliferated and remained viable for an extended period of time in vitro. In order to evaluate the hormonal response of cells within the scaffolds, the recellularized scaffolds were treated with a modified 28-day hormone regimen to mimic the human menstrual cycle. At the end of 28 days, the cells within the endometrial scaffold expressed both estrogen and progesterone receptors. In addition, decidualization markers, IGFBP-1 and prolactin, were secreted upon addition of dibutyryl cyclic AMP indicative of a decidualization response. This 3D model of the endometrium provides a new experimental tool to study endometrial biology and drug testing. Summary SentencePrimary endometrial cells within a recellularized scaffold respond to a 28-day menstrual cycle.

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Towards the development of a bioengineered uterus: Comparison of different protocols for rat uterus decellularization

Cited by 98 publications

References 53 publications

Uterine Tissue Engineering and the Future of Uterus Transplantation

Uterine Tissue Engineering and the Future of Uterus Transplantation

Uterus transplantation and beyond

Development of a novel human recellularized endometrium that responds to a 28-day hormone treatment†

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