Tissue Transplantation Research Articles

Conducting osteochondral injury model in rabbit knee: Pearls and pitfalls

Osteochondral damage is a commonly encountered issue in the daily orthopedic practice and has been extensively researched across various areas, including tissue transplantations, tissue engineering products, stem cell applications, and cell culture studies. The absence of a universally accepted treatment as the gold standard for osteochondral damage indicates the necessity for further studies in this field in the future. Although the biomechanical characteristics of the rabbit knee do not perfectly mimic those of the human knee, experimental studies conducted on rabbit knees are considered the most practical experimental model for testing a well-constructed experimental hypothesis. Our article endeavors to impart our practical insights and experiences to researchers without experience whom seeking to design studies utilizing this model. We aim to offer valuable guidance for preoperative, operative, and postoperative considerations.•Rabbits used in osteochondral healing models should be at least 4 months old or older. Inducing damage in the trochlea is a well-established technique and relatively easy to apply.•Do not use pointy ended drills as it might create uneven damage. Do not place applied treatment agent in inappropriate level in relation to the surrounding cartilage surface.

The bioengineering of perfusable endocrine tissue with anastomosable blood vessels

Organ transplantation is a definitive treatment for endocrine disorders, but donor shortages limit the use of this technique. The development of regenerative therapies would revolutionize the treatment of endocrine disorders. As is the case for harvested organs, the ideal bioengineered graft would comprise vascularized endocrine tissue, contain blood vessels that could be anastomosed to host vessels, have stable blood flow, and be suitable for transplantation into various sites. Here, we describe a transplantable endocrine tissue graft that was fabricated by ex vivo perfusion of tricultured cell sheets (islet β-cells, vascular endothelial cells (vECs), and mesenchymal stem cells (MSCs)) on a vascularized tissue flap of in vivo origin. The present study has three key findings. First, mild hypothermic conditions enhanced the success of ex vivo perfusion culture. Specifically, graft construction failed at 37 °C but succeeded at 32 °C (mild hypothermia), and endocrine tissue fabricated under mild hypothermia contained aggregations of islet β-cells surrounded by dense vascular networks. Second, the construction of transplantable endocrine tissue by ex vivo perfusion culture was better achieved using a vascular flap (VF) than a muscle flap. Third, the endocrine tissue construct generated using a VF could be transplanted into the rat by anastomosis of the graft artery and vein to host blood vessels, and the graft secreted insulin into the host’s circulatory system for at least two weeks after transplantation. Endocrine tissues bioengineered using these techniques potentially could be used as novel endocrine therapies.

Цивилистические основания донорства

The authors reveal in the article the nature, the main idea of donor legal relations, legal relations in the sphere of transplantation of donor organs and tissues, pointing out the problems that have objectively developed in our legal order. In fact, transactions in the sphere of donation and transplantation exist, but there is no proper legal regulation of the emerging legal relations. The authors adhere to the position that a person has the right to dispose of his body provided that such disposal does not entail the donor’s death or disability, and has the right to a commensurate compensation, acting not as a payment, but as a compensation for the harm to health, which was or could be a consequence of entering into donor legal relations. The necessity of terminological unity of normative-legal regulation of these relations is shown. The main purpose of the work is to reveal the private legal nature of donation, donor legal relations and legal relations in the field of transplantation. An attempt is made to describe the system of transactions in donation, proper ways of defence, problems of correlation of tort and contractual claims in relation to donation are discussed. Foreign experience is touched upon, showing the uncertain steps of different legal orders towards a freer regulation of this sphere of social relations. Political-economic and moral reasoning on the necessity of transferring donation relations from the sphere of public law to private law, as well as from state regulation to free market is given. Attention is emphasised on a number of contradictions that require resolution in doctrine, legislation and judicial practice.

Ethical Issues of Organ Transplantation

Organ Transplantation involves a surgical procedure where in a new organ replaces a deteriorating or damaged organ in the human body, Heart, lungs, Kidneys are examples of such organs. They are composed of tissues and cells that work together to perform specific essential functions in the human body. In the present scenario, the transplantation of many organs between well-matched human beings is marked with huge success. Heart and lung or heart-lung transplants, liver and pancreas (or pancreatic islets) transplants are also becoming more common, while kidney, cornea, bone marrow and skin transplants today are considered routine for certain conditions. According to Dr. Robert White, even a human head transplant, which should perhaps be better referred to as a body transplant, may be possible. However the balance between demand and supply is hugely distorted, marked simultaneously by high costs of some organ transplants. Consequently numerous questions come up today regarding procurement, distribution of scarce resources, and their coverage by community funds. The ethical and legal issues related to organ and tissue procurement and transplantation are often discussed in light of age old principles of autonomy, compassion, non-maleficence, free and informed consent, dignity, integrity and equality of human beings, justice, and the common good. "In the donation and transplantation of human organs, respect is to be given to the rights of the donor, the recipient and the common good of society”.

COVIDPOSTER 33C1q as pro-angiogenic factor in the context of ovarian tissue transplantation

COVIDPOSTER 33C1q as pro-angiogenic factor in the context of ovarian tissue transplantation

Determination Of Awareness and Knowledge Level on Brain Death, Organ Donation and Transplantation in Intensive Careers in Konya

Aim: It is shown that there is a lack of social and individual information on organ transplantation and donation, and as a result, organ donation is not sufficient due to social and individual insensitivity. In our study, we aimed to evaluate the level of awareness, attitude and knowledge about brain death, organ donation and transplantation in intensive care workers of hospitals in xxxx.
 Materials and Methods: A total of 219 healthcare professionals, 144 nurses and 75 doctors, who agreed to meet face-to-face with the researcher, who were working in xxxx province state hospitals, university hospitals and private hospital intensive care units, were included in the study. The data of the study were collected using the 'Data Collection Form', which was created as a result of the literature review and includes demographic information.
 Results: A total of 219 health care workers participated in the study with 144 (65.8%) intensive care nurses and 75 (34.2%) intensive care physicians. There was an organ donation card of 13.2% (n: 29) of the participants. There were 16,7% (n: 24) nurses and 6,7% (n: 5) doctor donation cards in doctors. In the case of brain death, 56.9% of participants wanted their organs to be donated. In the case of brain death, 58.7 of those who did not accept organ donation did not feel ready. 21% (n: 46) previously participated in organ / tissue donation and transplantation, 16.9% (n: 37) previously participated in brain death related trainings. Among the doctors who participated in the study 37.8% (n: 28) Electroencephalography (74%) and Radionuclide Cerebral Scintigraphy (62%) are the most common supportive tests used for the diagnosis of brain death.
 Discusion: Nursing and doctors' support of tissue / organ donation and transportation does not affect having donation card. There is no significant difference between the general knowledge levels of anesthesia and other branch physicians about brain death, but anesthesia doctors have been found to be more experienced in diagnosing brain death. We believe that the positive attitudes of the intensive care workers on this subject and the sufficient level of knowledge will positively affect the amount of organ donation.

Coupled experimental and theoretical study of hydroxyapatite ceramics

Hydroxyapatite is a biomaterial that has great importance in the medical field and is commonly used as an implant to replace amputated bone in tissue and organ transplants and in drug delivery systems. Quantum chemistry is based on the density functional theory (DFT), which is an important tool for understanding structural arrangements and explaining the physicochemical properties of complexes. This work is mainly based on the synthesis of hydroxyapatite using the double-decomposition method. Fine hydroxyapatite powder was characterized by different techniques such as infrared spectroscopy, the X-ray diffraction method, scanning electron microscopy and density measurement. The crystalline microstructure of hydroxyapatite is hexagonal with lattice parameters a = b = 9.4260 Å and c = 6.8850 Å and space group P63/m. Hydroxyapatite has a porous surface particle morphology with a regular spherical shape. An agreement between the energies and the vibrational frequency of connection which are characteristic of the infrared spectrum. The geometry of the complex isolated using the DFT method was optimized in open air and in various solvents. Different functionals were chosen to determine the energies of excitation and the forces of the associated oscillator of the studied complex. Theoretical absorption spectra were obtained using the GaussView and Origin software programs.

3D Imaging of Striatal Transplants in a Small Animal Model of Huntington's Disease.

High-resolution imaging in small animal models of neurologic disease is a technical challenge. In a pilot project, we have explored a non-destructive synchrotron imaging technique for the 3D visualization of intracerebral tissue transplants in a well-established small animal model of Huntington's disease. Four adult female Sprague Dawley rats each received injections of 0.12 M quinolinic acid (QA) into two target positions in the left striatum, thus creating unilateral left-sided striatal lesions similar to those frequently seen in patients suffering from Huntington's disease. One week after lesioning, the animals received transplants prepared from whole ganglionic eminences (wGEs) obtained from 13- to 14-day-old rat embryos. Of the four lesioned animals, three received transplants of GNP-loaded cells and one animal received a transplant of naïve cells, serving as control. Post-mortem synchrotron-based microCT was used to obtain images of the neurotransplants. The images obtained of GNP-loaded tissue transplants at the synchrotron corresponded in size and shape to the histological images of transplants developed from naïve cells. Thus, we conclude that non-destructive synchrotron imaging techniques such as phase-contrast imaging are suitable to obtain high-resolution images of GNP-loaded tissue transplants.

Black phosphorus nanosheets enhance differentiation of neural progenitor cells for improved treatment in spinal cord injury

Stem cell transplantation holds great potential as a treatment option for nerve damage diseases. However, the therapeutic effects are significantly impeded by low survival rate and uncontrolled differentiation of stem cells. In this study, black phosphorus nanosheets (BPNs), which are biodegradable inorganic nanomaterials, are first revealed with remarkable abilities to regulate cellular redox homeostasis, enhance transplant survival rate of stem cells, and facilitate neural differentiation of neural progenitor cells (NPCs). These effects of BPNs are proved to be associated with the activation of nuclear factor erythroid 2-like 2 (Nrf2) pathways in NPCs. In vivo, BPNs-treated NPCs could effectively inhibit inflammatory response and neuronal apoptosis in the mice with spinal cord injury (SCI). In addition, BPNs-treated NPCs more effectively reduce glial scar formation and promote axon regeneration compared with natural NPCs in SCI site. These findings collectively support the therapeutic potentials of BPNs for advanced stem cell transplantation and neural tissue engineering in the future.

The activity of Matrix Metalloproteinase-2 (MMP-2) and Tissue Inhibitors of Metalloproteinase-2 (TIMP-2) that are associated with the degree of endometrioma tissue invasion transplanted onto the Chorioallantoic Membrane (CAM)

Background. One of the fundamental pathogenesis of endometriosis to grow and develop is to carry out a cellular invasion of the surrounding tissue where it attaches. The invasion process of endometriotic focus is linked with the activity of matrix metalloproteinases-2 (MMP-2) and tissue inhibitors of metalloproteinases-2 (TIMP-2). In this study, we used endometrioma tissue to be implanted in chick chorioallantoic membrane (CAM) as a medium culture model to reconstruct and evaluate the invasion process of endometriosis. Then the MMP-2, TIMP-2 and invasion pattern can be invitro observed. Methods. Endometrioma tissue fragments were taken from ovarian endometrioma patients, reproductive age, no medication and no malignancy who underwent laparoscopic surgery. Sample research was taken in consecutive and non-probability sampling. The tissue fragments were divided into 4-8 strips, each dimension of 2 x 2 mm2. Two strips were assessed for the activity of MMP-2. Two remaining strips were transplanted onto the CAM. After incubation for five days, the transplanted tissues were harvested for assessment of MMP-2 by gelatin zymography, TIMP-2 by western blot and histological assessment by hematoxylin-eosin staining. The assessment was carried out by two qualified biologists as an observer. Result. Twenty-four fragments of endometrioma have been collected from 24 endometrioma patients who underwent laparoscopy surgery. The average age was 31±5 years, the BMI was 22±3 kg/m2, the duration of infertility was 58 ± 3 months, and r-ASRM was 67±35. In CAM of transplanted endometriomas tissue, MMP-2 activity was positively correlated with TIMP-2 in a moderate relationship (rô = 0.56, p-value < 0.05), very weak positive correlation with invasion level (rô = 0.08, p-value >0.05). TIMP-2 expression was negatively correlated with invasion level in a strong relationship (rô = -0.35, p-value <0.05). The ratio between MMP-2/TIMP-2 was positively correlated with invasion level in a very strong relationship (rô = 0.72, p-value < 0.05). ICC (intraclass correlation coefficient) value was 0.96, and p-value= 0.01, CI 95%. It shows that there was high reliability between observers. Conclusion. The invasion level of endometrioma transplanted onto CAM was determined by the balance between MMP-2 and TIMP-2.

Toward Transplantation of Liver Organoids: From Biology and Ethics to Cost-effective Therapy.

Liver disease is a common cause of morbidity and mortality, and many patients would benefit from liver transplantation. However, because of a shortage of suitable donor livers, even of those patients who are placed on the donor liver waiting list, many do not survive the waiting time for transplantation. Therefore, alternative treatments for end-stage liver disease need to be explored. Recent advances in organoid technology might serve as a solution to overcome the donor liver shortage in the future. In this overview, we highlight the potential of organoid technology for cell therapy and tissue engineering approaches. Both organoid-based approaches could be used as treatment for end-stage liver disease patients. Additionally, organoid-based cell therapy can also be used to repair liver grafts ex vivo to increase the supply of transplantable liver tissue. The potential of both approaches to become clinically available is carefully assessed, including their clinical, ethical, and economic implications. We provide insight into what aspects should be considered further to allow alternatives to donor liver transplantation to be successfully clinically implemented.

Immune landscape in rejection of renal transplantation revealed by high-throughput single-cell RNA sequencing.

Background: The role of the cellular level in kidney transplant rejection is unclear, and single-cell RNA sequencing (scRNA-seq) can reveal the single-cell landscape behind rejection of human kidney allografts at the single-cell level. Methods: High-quality transcriptomes were generated from scRNA-seq data from five human kidney transplantation biopsy cores. Cluster analysis was performed on the scRNA-seq data by known cell marker genes in order to identify different cell types. In addition, pathways, pseudotime developmental trajectories and transcriptional regulatory networks involved in different cell subpopulations were explored. Next, we systematically analyzed the scoring of gene sets regarding single-cell expression profiles based on biological processes associated with oxidative stress. Results: We obtained 81,139 single cells by scRNA-seq from kidney transplant tissue biopsies of three antibody-mediated rejection (ABMR) patients and two acute kidney injury (AKI) patients with non-rejection causes and identified 11 cell types, including immune cells, renal cells and several stromal cells. Immune cells such as macrophages showed inflammatory activation and antigen presentation and complement signaling, especially in rejection where some subpopulations of cells specifically expressed in rejection showed specific pro-inflammatory responses. In addition, patients with rejection are characterized by an increased number of fibroblasts, and further analysis of subpopulations of fibroblasts revealed their involvement in inflammatory and fibrosis-related pathways leading to increased renal rejection and fibrosis. Notably, the gene set score for response to oxidative stress was higher in patients with rejection. Conclusion: Insight into histological differences in kidney transplant patients with or without rejection was gained by assessing differences in cellular levels at single-cell resolution. In conclusion, we applied scRNA-seq to rejection after renal transplantation to deconstruct its heterogeneity and identify new targets for personalized therapeutic approaches.

Diagnostic effectiveness of intraoperative express histological examination as a tool to take decisions on the extent of surgery for papillary thyroid cancer

Background. In case of the screening use of high-resolution ultrasound, the level of detecting thyroid neoplasms is about 25 % in the population. Ultrasound criteria are not enough to detect carcinoma. The following methods are used for the differential diagnosis of malignant thyroid neoplasms: ultrasound scans, computed tomography, fine-needle aspiration (FNA) biopsy, intraoperative express histological and histopathological examination. Some authors consider FNA to be the standard method for primary morphological diagnosis of thyroid nodes. It is not always possible to conduct FNA safely. Also, FNA cannot be a method of 100% morphological identification of a primary tumor. In such cases, the extent of the surgery will depend on the data obtained from the intraoperative express histological examination. Analysis of the diagnostic effectiveness of the express histological examination will help to take a decision on the need for it when choosing the extent of a surgery on the thyroid gland. Aim of the study: to evaluate the diagnostic efficiency of the intraoperative express histological method in the detection of papillary thyroid cancer on solitary nodes (Bethesda IV, V) and metastases of papillary thyroid cancer during surgery. Materials and methods. The results of intraoperative express histological and pathohistological examinations performed at the Ukrainian Scientific and Practical Center for Endocrine Surgery, Transplantation of Endocrine Organs and Tissues from 2018 to 2021 were analyzed. The sample included materials of surgeries on the thyroid gland in case of papillary cancer T1ab-2N0–1 and solitary nodes (Bethesda IV and Bethesda V) according to data obtained using FNA. The sample size in the study of regional metastasis included 220 examinations, 845 examinations in the “gray zone” (Bethesda IV — 465, Bethesda V — 380). Cases of discrepancy between the results of intraoperative express histological and final histopathological examinations were considered. The data was processed using the EZR v. 3.4.1 statistical analysis program. Results. The sensitivity of the express histological examination in case of detecting metastases of thyroid cancer is 72.2 % with the method specificity of 99.9 %. The diagnostic efficiency in detecting metastases of thyroid cancer is 89.1 %. When the express histological examination is used for Bethesda IV nodes, the sensitivity of the method is 8 % with a specificity of almost 100 %. The diagnostic efficiency of the express histological examination is even higher in case of Bethesda V: sensitivity of 47 % with the method specificity of almost 100 %. The values obtained correlate with international data. This testifies to the need for further improvement of the of intraoperative diagnosis method. Conclusions. The diagnostic efficiency of the intraoperative express histological examination for detecting metastases of papillary thyroid cancer in the selected group is 89.1 % with sensitivity of 72.2 % and specificity of 99.9 %. The diagnostic efficiency of intraoperative express histological examination for verification of thyroid cancer in case of Bethesda IV nodes is 63.9 % with sensitivity of 8.2 % and specificity of 99.6 %. The diagnostic efficiency of intraoperative express histological examination for verification of thyroid cancer in Bethesda V nodes is 63.4 % with sensitivity of 47.3 % and specificity of 99.2 %. The intraoperative express histological examination method makes it possible to take decisions on surgical tactics during surgery within the determined limits, so we believe it reasonable to further use and improve it.

Chronological and reproductive aging-associated changes in resistance to oxidative stress in post-reproductive female mice.

Effort toward reproduction is often thought to negatively influence health and survival. Reproduction has been shown to influence metabolism, but the pathways and mechanisms have yet to be thoroughly elucidated. In the current experiments, our aim was to dissect the role of young and old ovarian tissues in the response to oxidative stress, through changes in liver oxidative stress response proteins. Liver proteins were analyzed in control mice at 4, 13, and 27months of age and compared to 23-month-old mice which received young ovarian tissue transplants (intact or follicle-depleted) at 13months of age. In control mice, of the 29 oxidative stress response proteins measured, 31% of the proteins decreased, 52% increased, and 17% were unchanged from 13 to 27months. The greatest changes were seen during the period of reproductive failure, from 4 to 13months of age. In transplanted mice, far more proteins were decreased from 13 to 23months (93% in follicle-containing young ovary recipients; 62% in follicle-depleted young ovary recipients). Neither transplant group reflected changes seen in control mice between 13 and 27months. Estradiol levels in transplant recipient mice were not increased compared with age-matched control mice. The current results suggest the presence of a germ cell- and estradiol-independent ovarian influence on aging-associated changes in the response to oxidative stress, which is manifest differently in reproductive-aged adults and post-reproductive-aged mice. The results presented here separate chronological and ovarian aging and the influence of estradiol in the response to aging-associated oxidative stress and support a novel, estradiol-independent role for the ovary in female health and survival.

Longitudinal anellome dynamics inthe upper respiratory tract ofchildren with acute respiratory tract infections.

Anelloviruses (AVs) are ubiquitous in humans and are the most abundant components of the commensal virome. Previous studies on the diversity, transmission, and persistence of AVs mainly focused on the blood or transplanted tissues from adults; however, the profile of the anellome in the respiratory tract in children are barely known. We investigated the anellome profile and their dynamics in the upper respiratory tract from a cohort of children with acute respiratory tract infections (ARTIs). Different to that in adult, betatorquevirus is the most abundant genus, followed by alphatorquevirus. We found that the relative abundance of betatorquevirus was higher in earlier time points, and in contrast, the abundance of alphatorquevirus was higher in later time points; these results might suggest that betatorquevirus decreased with age and alphatorquevirus increased with age in childhood. No difference regarding the diversity and abundance of anellome was found between single and multiple ARTIs, consistent with the idea that AV is not associated with certain disease. Most AVs are transient, and a small proportion (8 per cent) of them were found to be possibly persistent, with persistence time ranging from 1 month to as long as 56 months. Furthermore, the individual respiratory anellome appeared to be unique and dynamic, and the replacement of existing AVs with new ones are common over different time points. These findings demonstrate that betatorquevirus may be the early colonizer in children, and the individual respiratory anellome is unique, which are featured by both chronic infections and AV community replacement.

Beneficial biological effects of Flavokawain A, a chalcone constituent from kava, on surgically induced endometriosis rat model

Ethnopharmacological relevanceShrub kava has long been grown and utilized, primarily in the South Pacific region, for ceremonial, religious, and social occasions. It has been used as a pain reliever and muscle relaxant in medicinal practices from the eighteenth century. Interestingly, relatively low incidence of lung cancer may attribute to the high consumption of kava products in this region. Aim of the studyKava extracts were used to produce the kava chalcones Flavokawain A, B and C, which have a variety of bioactivities. In the present study, we show that Flavokawain A has positive effects on endometriosis. Materials and methodsThe endometriosis rat model was surgically induced by the autologous transplantation of endometrial tissue. Rats were evaluated for clinical ratings and lesion volume following a 6-week Flavokawain A therapy. Peritoneal fluid and blood samples were taken and ELISA assay was used to measure the cytokines and chemokines levels. Transcriptional and expression levels of Akt, PI3K, NF-kB, iNOS, Bcl-2, Bax and caspase-3 were evaluated by Western blotting and RT-qPCR. Implanted tissue sections of the rats were also analyzed by immunofluorescent and histopathological staining. ResultsLesion volumes and adhesion scores were successfully decreased. Blood and peritoneal fluid levels of associated cytokines and chemokines were markedly down-regulated. Besides, Flavokawain A also mediated cell apoptosis of endometrial implants. Additionally, VEGF expression was reduced, which inhibited the angiogenesis process. As for the expression of Akt, p-Akt, PI3K, p-PI3K, and NF-kB in endometriosis lesions, Flavokawain A significantly reduced them. ConclusionFlavokawain A has beneficial effects on the surgically induced endometriosis rat model, by reducing inflammation, promoting apoptosis, and decreasing angiogenesis. Our findings suggest that these effects may be mediated through the regulation of PI3K/Akt and NF-κB signaling pathways.

Effects of resveratrol on HIF-1α/VEGF pathway and apoptosis in vitrified duck ovary transplantation

Preservation of ovarian tissues is an effective way to ensure genetic diversity of susceptible natural bird populations that are in danger of extinction. We examined whether the addition of the plant phenol resveratrol to vitrification solutions ameliorates the damaging effects of tissue hypoxia and reperfusion injury when the tissues are transplanted. Duck ovary tissues were frozen in the presence of varying concentrations of resveratrol in cryopreservation solutions and then transplanted under the renal capsules of 2-day-old Shelducks. Samples of the transplanted tissues were examined on days 3- and 9- post transplantation for activation of hypoxia-, antioxidant- and apoptosis-related gene expression and apoptosis. Resveratrol significantly increased expression of VEGF, HIF-1α, Nrf2, CAT and Bcl-2 mRNA and decreased BAX and Caspase-3 mRNA and reduced numbers of TUNEL-positive cells after vitrification and heterotopic ovarian transplantation. Resveratrol improved the antioxidant capacity, reduced apoptosis and activated the HIF-1α/VEGF pathway to promote angiogenesis 3- and 9-days following transplantation. These results indicated that the addition of resveratrol to vitrification solutions intended for long-term cryopreservation of ovary tissues improves survival in storage and the grafts following transplantation. This study provides a theoretical basis for the successful transplantation of avian ovarian tissue after vitrification.

Ferroptosis in Autologous Fat Transplantation: A New Hypothesis.

Autologous adipose tissue transplantation is widely used for cosmetic and reconstruction of various areas in the body, often to repair soft tissue volume loss or contoured deformation. However, the application of fat transplantation is limited by unstable and unpredictable volume retention rates. At present, promoting adipose tissue survival and inhibiting its death is the key to improve the effect of autologous fat transplantation. In this paper, we propose a hypothesis that ferroptosis exists in fat transplantation. The bases of this hypothesis include the following: (1) the association between ferroptosis and other programmed cell death; (2) the association between ferroptosis and ischemia-reperfusion injury; and (3) the use of ferroptosis inhibitors in the field of fat transplantation.

Hyperplastic Human Macromass Cartilage for Joint Regeneration.

Cartilage damage affects millions of people worldwide. Tissue engineering strategies hold the promise to provide off-the-shelf cartilage analogs for tissue transplantation in cartilage repair. However, current strategies hardly generate sufficient grafts, as tissues cannot maintain size growth and cartilaginous phenotypes simultaneously. Herein, a step-wise strategy is developed for fabricating expandable human macromass cartilage (macro-cartilage) in a 3D condition by employing human polydactyly chondrocytes and a screen-defined serum-free customized culture (CC). CC-induced chondrocytes demonstrate improved cell plasticity, expressing chondrogenic biomarkers after a 14.59-times expansion. Crucially, CC-chondrocytes form large-size cartilage tissues with average diameters of 3.25 ± 0.05mm, exhibiting abundant homogenous matrix and intact structure without a necrotic core. Compared with typical culture, the cell yield in CC increases 2.57 times, and the expression of cartilage marker collagen type II increases 4.70 times. Transcriptomics reveal that this step-wise culture drives a proliferation-to-differentiation process through an intermediate plastic stage, and CC-chondrocytes undergo a chondral lineage-specific differentiation with an activated metabolism. Animal studies show that CC macro-cartilage maintains a hyaline-like cartilage phenotype in vivo and significantly promotes the healing of large cartilage defects. Overall, an efficient expansion of human macro-cartilage with superior regenerative plasticity is achieved, providing a promising strategy for joint regeneration.

Revascularization of human ovarian grafts is not equally efficient from both sides of the ovarian cortex tissue

Objective: Ovarian tissue cryopreservation and transplantation is an emerging fertility preservation technology. Ovarian tissue transplantation can prevent premature ovarian insufficiency, but follicle loss in the early stage of ovarian tissue transplantation is still the limiting factor of the technique. Does revascularization of human ovarian grafts in a mouse model occur with equal efficiency from both sides of the cortex tissue?