Accelerated Bone Regeneration via Three-Dimensional Cell-Printed Constructs Containing Human Nasal Turbinate-Derived Stem Cells as a Clinically Applicable Therapy

Abstract

Stem cell transplantation is a promising therapeutic strategy that includes both cell therapy and tissue engineering for the treatment of many regenerative diseases; however, the efficacy and safety of stem cell therapy depend on the cell type used in therapeutic and translational applications. In this study, we validated the hypothesis that human nasal turbinate-derived mesenchymal stem cells (hTMSCs) are a potential therapeutic source of adult stem cells for clinical use in bone tissue engineering using three-dimensional (3D) cell-printing technology. hTMSCs were cultured and evaluated for clinical use according to their cell growth, cell size, and preclinical safety and were then incorporated into a multicompositional 3D bioprinting system and investigated for bone tissue regeneration in vitro and in vivo. Finally, hTMSCs were compared with human bone marrow-derived MSCs (hBMSCs), which are the most common stem cell type used in regenerative medicine. hTMSCs from three different donors showed greater and faster cell growth than hBMSCs from two different donors when cultured. The hTMSCs were smaller in size than the hBMSCs. Furthermore, the hTMSCs did not exhibit safety issues in immunodeficient mice. hTMSCs in 3D-printed constructs (3D-hTMSC) showed much greater viability, growth, and osteogenic differentiation potential in vitro than hBMSCs in 3D-printed constructs (3D-hBMSC). Likewise, 3D-hTMSC showed better cell survival and alkaline phosphatase activity and greater osteogenic protein expression than 3D-hBMSC upon subcutaneous implantation into the dorsal region of nude mice. Notably, in an orthotopic model involving implantation into a tibial defect in rats, implantation of 3D-hTMSC led to greater bone matrix formation and enhanced bone healing to a greater degree than implantation of 3D-hBMSC. The clinically reliable evidence provided by these results is underlined by the potential for rapid tissue regeneration and ambulation in bone fracture patients implanted with 3D-hTMSC.

Effect of Bone Morphogenic Protein-2-Loaded Mesoporous Strontium Substitution Calcium Silicate/Recycled Fish Gelatin 3D Cell-Laden Scaffold for Bone Tissue Engineering

“…Bone has a complex hierarchical structure with the capability of self-regeneration. The regenerating process of bone generally consists of three major steps which are known as the inflammatory stage, endochondral bone formation phase and lastly, the bone remodeling phase [1]. Bone remodeling is regulated simultaneously and rigorously via osteoclast resorption and osteoblast secretion [2].…”

Potential application of human neural crest-derived nasal turbinate stem cells for the treatment of neuropathology and impaired cognition in models of Alzheimer’s disease

“…Considering the frequency of turbinate surgery, it is possible to obtain a sufficient number of hNTSCs via in vitro expansion and provide hNTSCs for clinical application. hNTSCs showed a strong proliferation capacity and an ability to differentiate into multiple cell types in vitro and in vivo [21][22][23][24]. Moreover, hNTSCs exhibit preservation of multiple biological characteristics in culture, independent of donor and cell expansion conditions [22,25], and do not cause safety issues in immunodeficient mice [24].…”

“…hNTSCs showed a strong proliferation capacity and an ability to differentiate into multiple cell types in vitro and in vivo [21][22][23][24]. Moreover, hNTSCs exhibit preservation of multiple biological characteristics in culture, independent of donor and cell expansion conditions [22,25], and do not cause safety issues in immunodeficient mice [24]. These considerations make hNTSCs a valuable alternative source of MSCs for tissue regeneration and clinical trials for the treatment of AD.…”

Cosmetic, Biomedical and Pharmaceutical Applications of Fish Gelatin/Hydrolysates

“…Bone has the ability of self-regeneration due to the complex hierarchical structure, for that it assists as a prototype exemplary in tissue engineering [79]. Fish gelatin sponge was embedded in the femoral condyle of osteochondral defected rabbit, gel foams were biocompatible with little immune response [52].…”