Revascularization of human ovarian grafts is equally efficient from both sides of the cortex tissue

Kristensen, Stine Gry; Olesen, Hanna Ørnes; Zeuthen, Mette Christa; Pors, Susanne Elisabeth; Andersen, Claus Yding; Mamsen, Linn Salto

doi:10.1016/j.rbmo.2022.02.009

Cited by 6 publications

(4 citation statements)

References 4 publications

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“…In 2022, Christine et al conducted research to answer the question of whether re-angiogenesis of human ovarian grafts occurs with similar efficiency in both cortical tissue sides in a murine model. They transplanted frozen ovarian pieces into nude mice for 8 days and concluded that angiogenesis occurs from both cortical tissue sides (72).…”

Section: Discussionmentioning

confidence: 99%

Human ovarian tissue xenotransplantation in 3D-printed tissue trapper basket integrated with human umbilical cord mesenchymal stem cells

Ayoubipour,

Eimani,

Fathi

et al. 2024

Preprint

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Purpose The primary objective was to develop an artificial ovary, using a 3D printed scaffold made of polylactic acid (PLA) material which could potentially be used for fertility preservation. In ovarian tissue (OT) transplantation, it was essential to prioritize follicle viability by promoting ideal angiogenesis at the back of neck muscle rats to improve the chances of successful follicle development. Methods The study involved transplanting human frozen-thawed ovarian cortical pieces into 3D-printed PLA polymer baskets, with or without human umbilical cord mesenchymal stem cells (HUC-MSCs). Four groups were formed: control, ovarian transplantation), OT in 3D-printed baskets without stem cells (OT + D), and OT in 3D-printed baskets with HUC-MSCs (OT + D + C). Eighteen rats were divided into three transplantation groups, and grafts were implanted into their back muscles. After one week, comparisons were made between OT, OT + D, and OT + D + C with control groups. Histological and gene expression analyses, including CX37, CX43, KL, GDF9, and VEGF, were conducted to evaluate factors like angiogenesis, cell proliferation, and follicle development. Results The result showed that OT + D had the highest follicular growth (99.5%) and transition rate (74.95%). OT + D + C showed increased follicular survival, reduced mortality (p < 0.0001), and a higher percentage of primordial follicles (59.1%). UCMSCs' paracrine secretions likely preserved the follicular reserve. Additionally, OT + D + C exhibited significantly increased blood vessel number and diameter (p < 0.0001) compared to other groups. Conclusions The study conducted a comprehensive evaluation, analyzing factors such as graft recovery, follicular density, stromal integrity, angiogenesis, and gene expression to understand transplantation outcomes fully. It found that a 3D basket scaffold facilitates ovarian follicle development by promoting angiogenesis and aiding maturation. Furthermore, when combined with stem cells, the scaffold enhances follicular preservation, preventing cell death and maintaining viability through paracrine secretions.

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Section: Discussionmentioning

confidence: 99%

Human ovarian tissue xenotransplantation in 3D-printed tissue trapper basket integrated with human umbilical cord mesenchymal stem cells

Ayoubipour,

Eimani,

Fathi

et al. 2024

Preprint

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“…Scanned WSI files were analysed in the Visiopharm Integrator System (VIS) using the APP via the Visiopharm Author™ module. The APP used has been described earlier [ 21 , 45 ]. The APP automatically recognized the tissue as the ROI, and afterwards murine host tissue was manually excluded before running the APP.…”

Section: Methodsmentioning

confidence: 99%

Effects of needle puncturing on re-vascularization and follicle survival in xenotransplanted human ovarian tissue

Olesen¹,

Pors²,

Adrados³

et al. 2023

Reprod Biol Endocrinol

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Background Ovarian tissue transplantation can restore fertility in young cancer survivors, however the detrimental loss of follicles following transplantation of cryopreserved ovarian tissue is hampering the efficiency of the procedure. This study investigates whether needle puncturing prior to transplantation can enhance revascularization and improve follicle survival in xenotransplanted human ovarian cortex. Methods Cryopreserved human ovarian cortex pieces (N = 36) from 20 women aged 24–36 years were included. During the thawing process, each piece of tissue was cut in halves; one half serving as the untreated control and the other half was punctured approximately 150–200 times with a 29-gauge needle. The cortex pieces were transplanted subcutaneously to immunodeficient mice for 3, 6 and 10 days (N = 8 patients) and for 4 weeks (N = 12 patients). After 3, 6 and 10 days, revascularization of the ovarian xenografts were assessed using immunohistochemical detection of CD31 and gene expression of angiogenic factors (Vegfα, Angptl4, Ang1, and Ang2), and apoptotic factors (BCL2 and BAX) were performed by qPCR. Follicle density and morphology were evaluated in ovarian xenografts after 4 weeks. Results A significant increase in the CD31 positive area in human ovarian xenografts was evident from day 3 to 10, but no significant differences were observed between the needle and control group. The gene expression of Vegfα was consistently higher in the needle group compared to control at all three time points, but not statistically significant. The expression of Ang1 and Ang2 increased significantly from day 3 to day 10 in the control group (p < 0.001, p = 0.0023), however, in the needle group this increase was not observed from day 6 to 10 (Ang2 p = 0.027). The BAX/BCL2 ratio was similar in the needle and control groups. After 4-weeks xenografting, follicle density (follicles/mm3, mean ± SEM) was higher in the needle group (5.18 ± 2.24) compared to control (2.36 ± 0.67) (p = 0.208), and a significant lower percentage of necrotic follicles was found in the needle group (19%) compared to control (36%) (p = 0.045). Conclusions Needle puncturing of human ovarian cortex prior to transplantation had no effect on revascularization of ovarian grafts after 3, 6 and 10 days xenotransplantation. However, needle puncturing did affect angiogenic genes and improved follicle morphology.

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“…Recently, Kristensen et al. reported that revascularization does not need this orientation, which reduces the time of the surgery as well ( 20 ).…”

Section: The Daily Routine Of a Cryobank Including Thawing And Transp...mentioning

confidence: 99%

“…Previously, the grafts were orientated with the outer cortex toward the tube. Recently, Kristensen et al reported that revascularization does not need this orientation, which reduces the time of the surgery as well (20).…”

Section: Thawing Servicementioning

confidence: 99%

Setup of a cryobank for ovarian tissue in a university-based setting

Baston-Büst,

Scheliga,

Bielfeld

2023

Front. Endocrinol.

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Establishing and maintaining a newly set-up cryobank for ovarian tissue in a university setting requires at least 1 year’s notice to start financial, spatial, lab equipment, and employee acquisition planning. Right before and after the start of the cryobank, the newly founded team should introduce itself to the hospitals and local and national health systems via mail, print flyers, and symposia in order to share the possibilities and the knowledge. Potential referrers should be provided with standard operating procedures and advice on getting used to the new system. Especially in the first year after the establishment, all procedures should be internally audited in order to avoid possible difficulties.

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Revascularization of human ovarian grafts is equally efficient from both sides of the cortex tissue

Cited by 6 publications

References 4 publications

Human ovarian tissue xenotransplantation in 3D-printed tissue trapper basket integrated with human umbilical cord mesenchymal stem cells

Human ovarian tissue xenotransplantation in 3D-printed tissue trapper basket integrated with human umbilical cord mesenchymal stem cells

Effects of needle puncturing on re-vascularization and follicle survival in xenotransplanted human ovarian tissue

Setup of a cryobank for ovarian tissue in a university-based setting

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