Developing a morphomics framework to optimize implant site-specific design parameters for islet macroencapsulation devices

Delivering a clinically impactful cell number is a major design challenge for cell macroencapsulation devices for Type 1 diabetes. It is important to understand the transplant site anatomy to design a device that is practical and that can achieve a sufficient cell dose. We identify the posterior rectus sheath plane as a potential implant site as it is easily accessible, can facilitate longitudinal monitoring of transplants, and can provide nutritive support for cell survival. We have investigated this space using morphomics across a representative patient cohort (642 participants) and have analysed the data in terms of gender, age and BMI. We used a shape optimization process to maximize the volume and identified that elliptical devices achieve a clinically impactful cell dose while meeting device manufacture and delivery requirements. This morphomics framework has the potential to significantly influence the design of future macroencapsulation devices to better suit the needs of patients.

Exploring Insulin Production Following Alveolar Islet Transplantation (AIT)

Recent studies have demonstrated the feasibility of islet implantation into the alveoli. However, until today, there are no data on islet behavior and morphology at their transplant site. This study is the first to investigate islet distribution as well insulin production at the implant site. Using an ex vivo postmortem swine model, porcine pancreatic islets were isolated and aerosolized into the lung using an endoscopic spray-catheter. Lung tissue was explanted and bronchial airways were surgically isolated and connected to a perfusor. Correct implantation was confirmed via histology. The purpose of using this new lung perfusion model was to measure static as well as dynamic insulin excretions following glucose stimulation. Alveolar islet implantation was confirmed after aerosolization. Over 82% of islets were correctly implanted into the intra-alveolar space. The medium contact area to the alveolar surface was estimated at 60 +/− 3% of the total islet surface. The new constructed lung perfusion model was technically feasible. Following static glucose stimulation, insulin secretion was detected, and dynamic glucose stimulation revealed a biphasic insulin secretion capacity during perfusion. Our data indicate that islets secrete insulin following implantation into the alveoli and display an adapted response to dynamic changes in glucose. These preliminary results are encouraging and mark a first step toward endoscopically assisted islet implantation in the lung.

Pre- and peri-operative factors influence autogenous tooth transplantation healing in insufficient bone sites

Background The amount of bone remaining at the transplant site for autogenous tooth transplantation can facilitate successful healing. Therefore, this retrospective study evaluated the factors influencing the healing of 50 successful autogenous tooth transplantations with insufficient bone support at the transplanted site without a bone graft. Methods The factors were classified as pre- and peri-operative factors, and the healing outcomes were clinical and radiographic observations. The factors were statistically analyzed using the chi-square test to identify correlations between the pre- and peri-operative factors and the clinical and radiographic outcomes. The T-test or one-way analysis of variance was used to compare the percent bone change in each factor. Results The results indicated that gingival healing was delayed in the intra-arch transplantations, and pulp obliteration was seen earlier when transplanted in the maxilla. Patients under 18-years-old demonstrated a greater percent bone change than the over 18-year-old patients, while the peri-operative variables did not have a relationship with clinical healing and the amount of bone change over 12 months. Furthermore, the percent bone change significantly increased during the first three months. Conclusions In conclusion, pre-operative factors, age and transplant site, influenced the healing rate of autogenous transplanted teeth. In contrast, the peri-operative factors were not related with the clinical and radiographic outcomes. Generating the least trauma to the periodontal ligament cells is the most important concern.

Exploring support persons' narrative accounts of waiting for lung transplant

Patients must have one designated support person (e.g., family member) provide constant care during the waiting period for lung transplant - this may involve relocation to be within 2.5 hours from the transplant site. There is little research concerning support persons’ experiences of waiting for transplant. This narrative study involving interviews and journaling, framed by the concept of liminality was conducted to explore support persons’ accounts of waiting for lung transplant. Findings indicate that support persons entered into a liminal space where they became focused upon and confined to patients’ routines and needs. The uncertainty of waiting was interwoven with emotions of hope, fear, and isolation. Implications include the need to identify the support person as a care recipient and implement supportive and counselling interventions responsive to their needs. This research also advances the theoretical concept of liminality in illness and provides direction for future research, policy and education

Exploring support persons' narrative accounts of waiting for lung transplant

Patients must have one designated support person (e.g., family member) provide constant care during the waiting period for lung transplant - this may involve relocation to be within 2.5 hours from the transplant site. There is little research concerning support persons’ experiences of waiting for transplant. This narrative study involving interviews and journaling, framed by the concept of liminality was conducted to explore support persons’ accounts of waiting for lung transplant. Findings indicate that support persons entered into a liminal space where they became focused upon and confined to patients’ routines and needs. The uncertainty of waiting was interwoven with emotions of hope, fear, and isolation. Implications include the need to identify the support person as a care recipient and implement supportive and counselling interventions responsive to their needs. This research also advances the theoretical concept of liminality in illness and provides direction for future research, policy and education

Preferable Transplant Site for Hepatocyte Transplantation in a Rat Model

Intraportal injection is regarded as the current standard procedure of hepatocyte transplantation (HTx). In islet transplantation, which shares many aspects with HTx, recent studies have clarified that instant blood-mediated inflammatory reaction (IBMIR), characterized by strong innate immune responses, can cause poor engraftment, so other transplant sites to avoid such a reaction have been established. Although IBMIR was reported to occur in HTx, few reports have evaluated alternative transplant sites for HTx. In this study, we sought to determine the optimum transplant site for HTx. Rat hepatocytes (1.0 × 107) were transplanted at the 9 transplant sites (intraportal (IPO), intrasplenic (IS), liver parenchyma, subcutaneous, intraperitoneal, renal subcapsular, muscle, inguinal subcutaneous white adipose tissue, and omentum) of analbuminemic rats. The serum albumin levels, immunohistochemical staining (albumin, TUNEL, and BrdU), and in vivo imaging of the grafts were evaluated. The serum albumin levels of the IPO group were significantly higher than those of the other groups ( p < .0001). The BrdU-positive hepatocyte ratio of liver in the IS group (0.9% ± 0.2%) was comparable to that of the IPO group (0.9% ± 0.3%) and tended to be higher than that of the spleen in the IS group (0.5% ± 0.1%, p = .16). Considering the in vivo imaging evaluation and the influence of splenectomy, the graft function in the IS group may be almost entirely achieved by hepatocytes that have migrated to the liver. The present study clearly showed that the intraportal injection procedure is more efficient than other procedures for performing HTx

Challenges in stem cell-derived islet replacement therapy can be overcome

In this Commentary, we echo the conclusions of a recent review titled “ The promise of stem cell-derived islet replacement therapy,” which highlighted recent advances in producing glucose responsive “islets” from stem cells and the benefits of their use in islet transplant therapy in type 1 diabetes (T1D). The review also outlined the status of clinical islet transplantation and the challenges that have prevented it from reaching its full therapeutic promise. We agree with the conclusions of the review and suggest that the identified challenges may be overcome by using the eye anterior chamber as an islet transplant site. We anticipate that the combination of stem cell-derived islets and intraocular transplant could help this promising T1D therapy reach full fruition.

White Adipose Tissue as a Site for Islet Transplantation

Although islet transplantation is recognized as a useful cellular replacement therapy for severe diabetes, surgeons face difficulties in islet engraftment. The transplant site is a pivotal factor that influences the engraftment. Although the liver is the current representative site for clinical islet transplantation, it is not the best site because of limitations in immunity, inflammation, and hypoxia. White adipose tissue, including omentum, is recognized as a useful candidate site for islet transplantation. Its effectiveness has been evaluated in not only various basic and translational studies using small and large animals but also in some recent clinical trials. In this review, we attempt to shed light on the characteristics and usefulness of white adipose tissue as a transplant site for islets.