The influence of systemically or locally administered mesenchymal stem cells on tissue repair in a rat oral implantation model

Abstract

BackgroundMultipotent mesenchymal stem cells (MSCs) are used clinically in regenerative medicine. Our previous report showed systemically injected MSCs improved peri-implant sealing and accelerated tissue healing. However, the risks of systemic MSC administration, including lung embolism, must be considered; therefore, their local application must be assessed for clinical safety and efficacy. We investigated differences in treatment effect between local and systemic MSC application using a rat oral implantation model.MethodsRat bone marrow-derived MSCs were isolated and culture-expanded. The rat’s right maxillary first molars were extracted and replaced with experimental titanium implants. After 24 h, MSCs (1 × 106/ml) were systemically or locally injected into recipient rats via the tail vein (systemic group) or buccal subcutaneous tissue (local group), respectively. Rats treated in the absence of MSCs were included as a control (control group). The maxillary epithelium was assessed histologically after 4 weeks to evaluate laminin-332 (Ln-332) distribution and horseradish peroxidase invasion, as indicators of peri-implant epithelium (PIE) formation and PIE sealing to the implant surface, respectively. The effect of MSCs on rat oral epithelial cell (OEC) morphology was determined by coculture.ResultsSystemic group MSCs accumulated early at the peri-implant mucosa, while local group MSCs were observed in various organs prior to later accumulation around the implant surface. PIE formation and Ln-332-positive staining at the implant interface were enhanced in the systemic group compared with the local and control groups. Furthermore, OEC adherence on implants was reduced in high-density compared with low-density MSC cocultures.ConclusionsLocal MSC injection was more ineffective than systemic MSC injection at enhancing PIE sealing around titanium implants. Thus, although local MSC administration has a wide range of applications, further investigations are needed to understand the exact cellular and molecular mechanisms of this approach prior to clinical use.

Novel Application Method for Mesenchymal Stem Cell Therapy Utilizing Its Attractant-Responsive Accumulation Property

“…Regarding the effect of administration method, we previously conducted a study comparing systemic and topical administration, which suggested that subcutaneous administration of MSCs was ineffective when not applied with a scaffold [28]. Similar to previous findings [36,37], the lung and liver accumulated many cells from the systemic circulation.…”

“…Both groups showed similar promotion of wound healing after tooth extraction, compared with both control groups ( Figure 5C). On the contrary, we recently reported that the high density of MSCs at the injected site following local administration meant that it was hard for them to move from the administration site to the site of inflammation [28].…”

“…We previously reported that intravenous administration of MSCs in rats contributed to the healing of damaged tissue [27]. However, delivering cells subcutaneously without a scaffold did not result in a positive effect on tissue healing [28]. As such, we focused on the scaffold as a foundation for cells.…”

Insights into the use of mesenchymal stem cells in COVID-19 mediated acute respiratory failure

“…However, with all drug therapeutics, the mode of drug delivery and targeting strategy needs to be given serious consideration. Dependent on the indication, MSCs have been delivered via multiple routes of administration, from direct injection to IV delivery 83 . In the context of COVID-19-associated ARDS, MSCs need to exert their therapeutic effects in the lungs.…”

Applications of stem cells in dentistry: a review

“…To be classified as MSC, they must satisfy the minimum criteria set by the International Society for Cellular Therapy that they must be adherent to tissue culture treated plastic under ideal conditions and must be able to differentiate into adipocytes, chondroblasts and osteoblasts in-vitro (11). Although systemic administration of MSC carries a significant risk of pulmonary embolism and accumulation in healthy organs, Kanawaza et al found that it has a higher efficacy when compared to local administration (12).…”