• Clinical and Experimental Otorhinolaryngology
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• v.11 no.4
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• pp.224-232
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• 2018

Objectives. Spiral ganglion neurons (SGNs) include potential endogenous progenitor populations for the regeneration of the peripheral auditory system. However, whether these populations are present in adult mice is largely unknown. We examined the presence and characteristics of SGN-neural stem cells (NSCs) in mice as a function of age. Methods. The expression of Nestin and Ki67 was examined in sequentially dissected cochlear modiolar tissues from mice of different ages (from postnatal day to 24 weeks) and the sphere-forming populations from the SGNs were isolated and differentiated into different cell types. Results. There were significant decreases in Nestin and Ki67 double-positive mitotic progenitor cells in vivo with increasing mouse age. The SGNs formed spheres exhibiting self-renewing activity and multipotent capacity, which were seen in NSCs and were capable of differentiating into neuron and glial cell types. The SGN spheres derived from mice at an early age (postnatal day or 2 weeks) contained more mitotic stem cells than those from mice at a late age. Conclusion. Our findings showed the presence of self-renewing and proliferative subtypes of SGN-NSCs which might serve as a promising source for the regeneration of auditory neurons even in adult mice.

• Polymer(Korea)
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• v.38 no.2
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• pp.113-128
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• 2014

Tissue engineering and regenerative medicine strategies could offer new hope for patients with serious tissue injuries or end-stage organ failure. Scientists are now applying the principles of cell transplantation, material science, and engineering to create biological substitutes that can restore and maintain normal function in diseased or injured tissues/organs. Specifically, creation of engineered tissue construct requires a polymeric biomaterial scaffold that serves as a cell carrier, which would provide structural support until native tissue forms in vivo. Even though the requirements for scaffolds may be different depending on the target applications, a general function of scaffolds that need to be fulfilled is biodegradability, biological and mechanical properties, and temporal structural integrity. The scaffold's internal architecture should also enhance the permeability of nutrients and neovascularization. In addition, the stem cell field is advancing, and new discoveries in tissue engineering and regenerative medicine will lead to new therapeutic strategies. Although use of stem cells is still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous adult cells have already entered the clinic. This review discusses these tissue engineering and regenerative medicine strategies for various tissues and organs.

• BMB Reports
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• v.56 no.1
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• pp.10-14
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• 2023

Organoids derived from stem cells or organ-specific progenitors are self-organizable, self-renewable, and multicellular three-dimensional (3D) structures that can mimic the function and structure of the derived tissue. Due to such characteristics, organoids are attracting attention as an excellent ex vivo model for drug screening at the stage of drug development. In addition, since the applicability of organoids as therapeutics for tissue regeneration has been embossed, the development of various organoids-based regenerative medicine has been rapidly progressing, reaching the clinical trial stage. In this review, we give a general overview of organoids and describe current status and prospects of organoid-based regenerative medicine, focusing on organoid-based regenerative therapeutics currently under development including clinical trials.

• Polymer Science and Technology
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• v.22 no.1
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• pp.17-26
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• 2011

• Animal cells and systems
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• v.5 no.2
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• pp.91-99
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• 2001

Vertebrates regenerate tissues in three ways: proliferation of cells that maintain some or all of their differentiated structure and function, redifferentiation of mature cells followed by proliferation and redifferentiation into the same cell type or transdetermination to another cell type, and activation of restricted lineage stem cells, which have the ability to transdetermine to different lineages under the appropriate conditions. The behavior of the cells during regeneration is regulated by growth factors and extracellular matrix molecules. Some non-regenerating tissues are now known to harbor stem cells which, though they form scar tissue in vivo, are capable of producing new tissue-specific cells in vitro, suggesting that the injury environment inhibits latent regenerative capacity. Regenerative medicine seeks to restore tissues via transplantation of stem cell derivatives, implantation of bioartificial tissues, or stimulation of regeneration in vivo. These approaches have been partly successful, but several research issues must be addressed before regenerative medicine becomes a clinical reality.

• Childhood Kidney Diseases
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• v.23 no.2
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• pp.67-76
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• 2019

Kidney disease is a major global health issue. Hemodialysis and kidney transplantation have been used in the clinic to treat renal failure. However, the dialysis is not an effective long-term option, as it is unable to replace complete renal functions. Kidney transplantation is the only permanent treatment for end-stage renal disease (ESRD), but a shortage of implantable kidney tissues limits the therapeutic availability. As such, there is a dire need to come up with a solution that provides renal functions as an alternative to the current standards. Recent advances in cell-based therapy have offered new therapeutic options for the treatment of damaged kidney tissues. Particularly, cell secretome therapy utilizing bioactive compounds released from therapeutic cells holds significant beneficial effects on the kidneys. This review will describe the reno-therapeutic effects of secretome components derived from various types of cells and discuss the development of efficient delivery methods to improve the therapeutic outcomes.

• Yonsei Medical Journal
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• v.59 no.9
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• pp.1015-1025
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• 2018

Kidney diseases including acute kidney injury and chronic kidney disease are among the largest health issues worldwide. Dialysis and kidney transplantation can replace a significant portion of renal function, however these treatments still have limitations. To overcome these shortcomings, a variety of innovative efforts have been introduced, including cell-based therapies. During the past decades, advances have been made in the stem cell and developmental biology, and tissue engineering. As part of such efforts, studies on renal cell therapy and artificial kidney developments have been conducted, and multiple therapeutic interventions have shown promise in the pre-clinical and clinical settings. More recently, therapeutic cell-secreting secretomes have emerged as a potential alternative to cell-based approaches. This approach involves the use of renotropic factors, such as growth factors and cytokines, that are produced by cells and these factors have shown effectiveness in facilitating kidney function recovery. This review focuses on the renotropic functions of bioactive compounds that provide protective and regenerative effects for kidney tissue repair, based on the available data in the literature.

• Biomaterials and Biomechanics in Bioengineering
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• v.1 no.1
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• pp.27-39
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• 2014

We have previously described a new multilayer alginate microcapsule system, and the goals of the present study were to assess the in vitro function of islets encapsulated in its inner layer, and the angiogenic ability of FGF-1 delivered from the external layer in an omentum pouch. Following isolation and culture, islets were encapsulated in the inner core of microspheres ($500-600{\mu}m$ in diameter) with a semi-permeable poly-L-ornithine (PLO) membrane separating two alginate layers, and both unencapsulated and encapsulated islet function was assessed by a dynamic glucose perifusion. For angiogenesis experiments, one group of microcapsules without FGF-1 (control) and another (test) containing FGF-1 with heparin encapsulated in the external layer were made. One hundred microcapsules of each group were transplanted in Lewis rats (n = 5/group) and were retrieved after 14 days for assessment of angiogenesis. Glucose perifusion of unencapsulated and encapsulated islets resulted in similar stimulation indices. The release of FGF-1 resulted in increased vascular density compared to controls. In conclusion, islets encapsulated in the core of multilayer alginate microcapsules maintain functionality and the microcapsule's external layer is effective in delivery of FGF-1 to enhance graft neovascularization in a retrievable omentum pouch.

• Tissue Engineering and Regenerative Medicine
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• v.15 no.6
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• pp.751-760
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• 2018

BACKGROUND: Bone tissue engineering based on pluripotent stem cells (PSCs) is a new approach to deal with bone defects. Protocols have been developed to generate osteoblasts from PSCs. However, the low efficiency of this process is still an important issue that needs to be resolved. Many studies have aimed to improve efficiency, but developing accurate methods to determine efficacy is also critical. Studies using pluripotency to estimate efficacy are rare. Telomerase is highly associated with pluripotency. METHODS: We have described a quantitative method to measure telomerase activity, telomeric repeat elongation assay based on quartz crystal microbalance (QCM). To investigate whether this method could be used to determine the efficiency of in vitro osteogenic differentiation based on pluripotency, we measured the pluripotency pattern of cultures through stemness gene expression, proliferation ability and telomerase activity, measured by QCM. RESULTS: We showed that the pluripotency pattern determined by QCM was similar to the patterns of proliferation ability and gene expression, which showed a slight upregulation at the late stages, within the context of the general downregulation tendency during differentiation. Additionally, a comprehensive gene expression pattern covering nearly every stage of differentiation was identified. CONCLUSION: Therefore, this assay may be powerful tools for determining the efficiency of differentiation systems based on pluripotency. In this study, we not only introduce a new method for determining efficiency based on pluripotency, but also provide more information about the characteristics of osteogenic differentiation which help facilitate future development of more efficient protocols.

• The Korean Journal of Physiology
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• v.11 no.2
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• pp.9-16
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• 1977

The present experiment was conducted to see whether or not several cardioactive agents influence the 'regenerative $Ca^{++}$ release' in the mechanically disrupted cardiac cells. The mechanically disrupted cardiac cells were prepared by the method of Kerrick and Best from the ventricle of rat. The tension development of the disrupted cardiac cells was measured with a mechanoelectric transducer (RCA 5734). The results were summarized as follows 1) 2 mM caffeine enhanced the regenerative $Ca^{++}$ release, whereas 2 mM Procaine inhibited the $Ca^{++}$ release as reported by other investigators. 2) Epinephrine at concentrations of $10^{-7},\;10^{-6}\;and\;10^{-5}M$ increased the regenerative $Ca^{++}$ release significantly but showed a poor dose response on the $Ca^{++}$ release. 3) Propranolol showed no effect on the regenerative $Ca^{++}$ release when studied alone. Furthermore, it showed no antagonistic effect on an increased regenerative $Ca^{++}$ release induced by epinephrine. 4) Other cardioactive agents such as acetylcholine, ouabain, isoproterenol and c-AMP at concentrations of $10^{-6}M$ showed no effect on the regenerative $Ca^{++}$ release. From the above results, it may be concluded that the cardioactive actions of these agents are not related directly to the process of regenerative $Ca^{++}$ release.