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.
Highlights
Multipotent mesenchymal stem cells (MSCs) are used clinically in regenerative medicine
Because the systemically injected MSCs accumulated around the experimental implant, we believe they acted through both regenerative medicine and cell therapy modes [1]
For a number of other factors need consideration, including cell source, cell donor condition, cell population, and timing of MSC administration, this study only focused on comparison between systemic and local injection of MSCs into a rat oral implant model
Summary
Multipotent 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. Mesenchymal stem cell (MSC)-based approaches can be broadly divided into two categories: cell therapy and regenerative medicine. Regenerative medicine is focused on MSCs playing a tissue engineering role, to enhance tissue regeneration using growth factors and scaffolds; for example, to generate tissue-engineered skin or cartilage, which have been assessed in clinical trials. Our previous study showed that systemically injected MSCs improved attachment of the peri-implant epithelium (PIE) to the titanium (Ti) implant surface and accelerated tissue healing around the implant. Because the systemically injected MSCs accumulated around the experimental implant, we believe they acted through both regenerative medicine and cell therapy modes [1]. Improving local defense within the mucosa is indispensable to enabling successful implantation
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