Human gingival mesenchymal stem cells retain their growth and immunomodulatory characteristics independent of donor age.

Aging has been reported to deteriorate the quantity and quality of mesenchymal stem cells (MSCs), which affect their therapeutic use in regenerative medicine. A dearth of age-related stem cell research further restricts their clinical applications. The present study explores the possibility of using MSCs derived from human gingival tissues (GMSCs) for studying their ex vivo growth characteristics and differentiation potential with respect to donor age. GMSCs displayed decreased in vitro adipogenesis and in vitro and in vivo osteogenesis with age, but in vitro neurogenesis remained unaffected. An increased expression of p53 and SIRT1 with donor age was correlated to their ability of eliminating tumorigenic events through apoptosis or autophagy, respectively. Irrespective of donor age, GMSCs displayed effective immunoregulation and regenerative potential in a mouse model of LPS-induced acute lung injury. Thus, we suggest the potential of GMSCs for designing cell-based immunomodulatory therapeutic approaches and their further extrapolation for acute inflammatory conditions such as acute respiratory distress syndrome and COVID-19.

Hydroxyapatite nanorods loaded with parathyroid hormone (PTH) synergistically enhance the net formative effect of PTH anabolic therapy.

Parathyroid hormone (PTH) has been a major contributor to the anabolic therapy for osteoporosis, but its delivery to bone without losing activity and avoiding adverse local effects remain a challenge. Being the natural component of bone, use of hydroxyapatite for this purpose brings a major breakthrough in synergistic anabolism. This study focuses on synthesis, characterization and evaluation of in vitro and in vivo efficacy of PTH (1-34) adsorbed hydroxyapatite nanocarrier for synergistic enhancement in the anabolic activity of PTH for bone regeneration. The negative zeta potential of this nanocarrier facilitated its affinity to the Ca2+ rich bone tissue and solubilization at low pH enhanced specific delivery of PTH to the resorption pits in osteoporotic bone. In this process, PTH retained its anabolic effect and at the same time an increase in bone mineral content indicated enhancement of the net formative effect of the PTH anabolic therapy.

Scaffold-Free Spheroids Derived from Stem Cells for Tissue-Engineering Applications.

Tissue engineering has gained attention in the past decade due to its efficient interaction with the host system and potential therapeutic capabilities. Although scaffold-based approaches provide much needed mechanical strength and support to the regenerating tissue, they also invite foreign body reaction initiated by macrophages, causing inflammation and toxicity, and may also sometime interfere with the regeneration of indigenous tissue due to very slow degradation. Therefore, spheroids provide a promising tool for improving cell survival and for preserving cell-to-cell interaction. They have promptly gained popularity because of their ability to provide superior cellular heterogeneity, nutrient and oxygen gradients (replicating the original tissue), matrix deposition, and gene expression profiles. Because of their ability to differentiate into multiple cell lineages, stem cell-based spheroids have opened new avenues for future regenerative medicine. In this review we focus on various methods for fabrication of spheroids from stem cells and their application in regenerative approaches for different tissues/organs.

Dental Tissue-Derived Mesenchymal Stem Cells: Applications in Tissue Engineering.

In recent years, mesenchymal stem cells (MSCs) derived from dental tissue have gained in popularity for tissue-engineering and regenerative medicine applications. The highly proliferative and self-renewing population of dental stem cells has the neural crest as their origin. This expands their applicability for regeneration of tissues from both ectochyme and mesenchymal origin. Ease of tissue harvest, high initial yield of cells, low population-doubling time, plasticity, multipotential capabilities, and immunomodulatory properties make them a suitable candidate for various therapeutic strategies. Furthermore, dental tissue-derived cells can be transformed into induced pluripotent stem cells to customize cell-based regenerative approaches. However, there is currently a lack of exhaustive comparative profiles of these dental tissues and their regenerative applications. We thereby present a comprehensive compilation of morphofunctional analyses and tissue-engineering applications of MSCs that are derived from tooth germ, exfoliated deciduous teeth, periodontal ligament, gingiva, dental pulp, alveolar bone, dental follicle, and apical papilla. Immunoregulatory properties of dental stem cells provide potential for both autologous and allogenic tissue-engineering approaches. In vitro and animal studies show promise for using dental stem cells in regenerative medicine. Eventually, the orchestration of clinical trials will require systematic monitoring of spontaneous in vitro transformations and complications associated with graft versus host response as well as a thorough understanding of underlying anabolic mechanisms.