Human adipose-derived stromal/stem cells demonstrate short-lived persistence after implantation in both an immunocompetent and an immunocompromised murine model

Abstract

IntroductionMesenchymal cells are emerging as a promising cell platform for regenerative therapies. However, the fate of cells after transplantation in many different disease settings and tissue beds remains unclear.MethodsIn this study, human adipose-derived stromal/stem (ASCs) cells were fluorescently labeled with a membrane dye and injected into both immunocompetent and immunocompromised mouse strains. Cells were injected either as single cell suspensions, or as self-assembling spheroids. In parallel, cells were purposefully devitalized prior to injection and then implanted in the opposite side in a randomized fashion. These ‘control’ groups were included to determine whether the fluorescent membrane dye would remain localized at the injection site despite the use of nonviable cells. Cell implants and the surrounding tissues were harvested on days 3, 10 and 21 after in vivo delivery and evaluated in a blinded manner. Injection sites were analyzed by fluorescent microscopy, and human cell numbers were quantified using PCR detection of a human-specific endogenous retrovirus (ERV-3). Host response was evaluated by immunofluorescent staining of macrophages.ResultsERV-3 quantification showed that 95% of the human cells that were viable when they were injected were undetectable at the three-week time-point. Although fluorescent signal persisted for the entire study period, further analysis revealed that much of this signal was located within host macrophages.ConclusionsThese results suggest that human ASCs survive for less than three weeks after injection into even immunocompromised mice, and call into question the notion that human ASCs are immuno-privileged and capable of surviving for extended periods in xenogeneic and/or allogeneic models.

Precise injection of human mesenchymal stromal cells in the urethral sphincter complex of Göttingen minipigs without unspecific bulking effects

“…But it has to be stated clearly that as early as three weeks after MSC injection, DNA extracted from the HE‐positive cellular depots did not yield sufficient products by polymerase chain reactions (PCR, not shown). This is in line with recent reports indicating that injected cells can be detected only for a short period of time after application . In contrast, in our study many MSCs remained at the spot of application and wasted, possibly by factor deprivation.…”

“…An optimal dispersion of the cells is important for the outcome of such therapies. Recent studies suggested that MSCs injected in muscular tissues may migrate and leave the injection site over time . In our study neo‐vascularization was not observed in the area of cell injection in any of the animals investigated, although MSC may facilitate neovascularization …”

Monitoring of diffusion properties and transverse relaxation time of mouse ischaemic muscle after administration of human mesenchymal stromal cells derived from adipose tissue

“…Agrawal, et al (2014) showed that hADSCs transplanted into subcutaneous and inguinal fat pad do not persist for longer than 3 weeks (90% reduction in cells number by day 10) in immunocompromised mice, while the clearance rate for immunocompetent recipients is faster. Of note, short survival time was associated with macrophage infiltration even in immunodeficient mice . Results from our laboratory indicate that hADSCs were still present in the gastrocnemius muscles of the injured limbs at 14 days after delivery …”

A new composite hydrogel combining the biological properties of collagen with the mechanical properties of a supramolecular scaffold for bone tissue engineering

“…This is a major and original property of this new composite gel. Indeed, several in vivo studies, addressing the fate of biomaterial‐associated cells after their implantation, have revealed the loss of the majority of cells within 10–14 days (Agrawal et al, ). We assume that this behaviour is due to the composite gel capacity to by one side provide adhesion sites to cells, within the collagen matrix, while preventing cell migration, due to the GNF fraction.…”