Enhancing Immunomodulatory Function of Mesenchymal Stromal Cells by Hydrogel Encapsulation.

Mesenchymal stromal cells (MSCs) showcase remarkable immunoregulatory capabilities in vitro, positioning them as promising candidates for cellular therapeutics. However, the process of administering MSCs and the dynamic in vivo environment may impact the cell-cell and cell-matrix interactions of MSCs, consequently influencing their survival, engraftment, and their immunomodulatory efficacy. Addressing these concerns, hydrogel encapsulation emerges as a promising solution to enhance the therapeutic effectiveness of MSCs in vivo.

Reciprocal Donor-Recipient Strain Combinations Present Different Vascularized Composite Allotransplantation Outcomes in Rodent Models.

Background: Although vascularized composite allotransplantation (VCA) has been the focus of many animal studies, further research is needed to determine the potential for a generalized model and immunosuppression regimen that applies across different donor-recipient combinations. In this study, the authors evaluated the outcome of VCAs performed on reciprocal rodent donor-recipient combinations.

Methods: VCA was performed in rats using Lewis and Brown Norway (BN) donor-recipient pairs, under the previously reported antilymphocyte serum/cyclosporine/adipose-derived stem cell regimen.

Preconditioned Mesenchymal Stromal Cells to Improve Allotransplantation Outcome.

Mesenchymal stromal cells (MSCs) are tissue-derived progenitor cells with immunomodulatory as well as multilineage differentiation capacities, and have been widely applied as cellular therapeutics in different disease systems in both preclinical models and clinical studies. Although many studies have applied MSCs in different types of allotransplantation, the efficacy varies. It has been demonstrated that preconditioning MSCs prior to in vivo administration may enhance their efficacy.

Predicting Outcomes of Rat Vascularized Composite Allotransplants through Quantitative Measurement of Chimerism with PCR-Amplified Short Tandem Repeat.

Chimerism has been associated with the induction and maintenance of tolerance to vascularized composite allotransplants (VCA). Although most VCA studies have examined chimerism using flow cytometry, we proposed that precision in the measurement of chimerism may be better approximated when complimentary polymerase chain reaction (PCR) is applied to a specific short tandem repeat (STR). We identified a STR, D10Rat25, which exhibited a ~20 bp difference in length between two rat strains (BN and LEW) often utilized as the donor and recipient in many allotransplantation studies.

Bioimaging of alloantigen-stimulated regulatory T cells in rat vascularized composite allotransplantation.

Background: Tipping the balance toward regulatory T cells (Tregs) through adoptive cell therapy has shown promise to induce transplantation tolerance. Although such strategy has been explored in many mice organ transplantation studies, less knowledge was available in rat systems. Furthermore, the behaviors of the transferred cells have not been well studied in real-time fashion.

A novel rat full-thickness hemi-abdominal wall/hindlimb osteomyocutaneous combined flap: influence of allograft mass and vascularized bone marrow content on vascularized composite allograft survival.

Vascularized bone marrow transplantation (VBMT) appears to promote tolerance for vascularized composite allotransplantation (VCA). However, it is unclear whether VBMT is critical for tolerance induction and, if so, whether there is a finite amount of VCA that VBMT can support. We investigated this with a novel VCA combined flap model incorporating full-thickness hemiabdominal wall and hindlimb osteomyocutaneous (HAW/HLOMC) flaps.

Syngeneic adipose-derived stem cells with short-term immunosuppression induce vascularized composite allotransplantation tolerance in rats.

Background Aims: A clinically applicable tolerance induction regimen that removes the requirement for lifelong immunosuppression would benefit recipients of vascularized composite allotransplantation (VCA). We characterized the immunomodulatory properties of syngeneic (derived from the recipient strain) adipocyte-derived stem cells (ADSCs) and investigated their potential to induce VCA tolerance in rats.

Methods: ADSCs were isolated from Lewis (LEW, RT1A(l)) rats; their immunomodulatory properties were evaluated by means of mixed lymphocyte reactions in vitro and VCAs in vivo across a full major histocompatibility complex mismatch with the use of Brown-Norway (BN, RT1A(n)) donor rats.