Platelet-rich fibrin (PRF) has been used in regenerative medicine and dentistry. Recently, its use has been advocated for regenerative periodontics and wound healing. The randomized control trials have assessed the regenerative efficacy of the PRF for restoring intrabony periodontal defects.The objectives are to critically analyze and appraise the currently available literature, focusing on the use of PRF in regenerating periodontal bone defects. An electronic search was conducted (PubMed/MEDLINE, Google Scholar, ISI-WOS). Various combinations of following keywords were used: ‘ platelet-rich fibrin’, ‘ intrabony’, ‘ periodontal’, ‘ bone defect’ and ‘ guided tissue regeneration’.Asecondary search was conducted by analyzing the reference lists of the articles obtained in initial search. The final search resulted in 13 randomized controlled trials being included. Inmajority of studies, PRF resulted in better clinical/radiographic outcomes than open flap debridement and augmented therapeutic effects of bone grafts. The combination of bovine bone substitutes and PRF resulted in better performance compared to alone. Similarly better outcomes were observed while using PRF in combination with nanohydroxyapatite, metformin and demineralized freeze-dried bone allograft. It can be concluded that PRF produces better outcomes than open flap debridement alone and augments the regenerative effects of bone substitutes.
Allografts ; Blood Platelets* ; Bone Substitutes ; Debridement ; Dentistry ; Fibrin* ; Metformin ; Periodontics ; Regeneration ; Regenerative Medicine ; Therapeutic Uses ; Tissue Engineering ; Transplants ; Wound Healing

Stem cell research is one of the most rapidly expanding field of medicine which provides significant opportunities for therapeutic and regenerative applications. Different types of stem cells have been isolated investigating their accessibility, control of the differentiation pathway and additional immunomodulatory properties. Bulk of the literature focus has been on the study and potential applications of adult stem cells (ASC) because of their low immunogenicity and reduced ethical considerations. This review paper summarizes the basic available literature on different types of ASC with special focus on stem cells from dental and orofacial origin. ASC have been isolated from different sources, however, isolation of ASC from orofacial tissues has provided a novel promising alternative. These cells offer a great potential in the future of therapeutic and regenerative medicine because of their remarkable availability at low cost while allowing minimally invasive isolation procedures. Furthermore, their immunomodulatory and anti-inflammatory potential is of particular interest. However, there are conflicting reports in the literature regarding their particular biology and full clinical potentials. Sound knowledge and higher control over proliferation and differentiation mechanisms are prerequisites for clinical applications of these cells. Therefore, further standardized basic and translational studies are required to increase the reproducibility and reduce the controversies of studies, which in turn facilitate comparison of related literature and enhance further development in the field.
Adult Stem Cells* ; Adult* ; Biology ; Humans ; Regenerative Medicine* ; Stem Cell Research ; Stem Cells

Electrospinning is a simple and versatile technique to fabricate continuous fibers with diameter ranging from micrometers to a few nanometers. To date, the number of polymers that have been electrospun has exceeded 200. In recent years, electrospinning has become one of the most popular scaffold fabrication techniques to prepare nanofiber mesh for tissue engineering applications. Collagen, the most abundant extracellular matrix protein in the human body, has been electrospun to fabricate biomimetic scaffolds that imitate the architecture of native human tissues. As collagen nanofibers are mechanically weak in nature, it is commonly cross-linked or blended with synthetic polymers to improve the mechanical strength without compromising the biological activity. Electrospun collagen nanofiber mesh has high surface area to volume ratio, tunable diameter and porosity, and excellent biological activity to regulate cell function and tissue formation. Due to these advantages, collagen nanofibers have been tested for the regeneration of a myriad of tissues and organs. In this review, we gave an overview of electrospinning, encompassing the history, the instrument settings, the spinning process and the parameters that affect fiber formation, with emphasis given to collagen nanofibers' fabrication and application, especially the use of collagen nanofibers in skin tissue engineering.
Biomimetics ; Collagen* ; Extracellular Matrix ; Human Body ; Humans ; Nanofibers* ; Polymers ; Porosity ; Regeneration ; Skin* ; Tissue Engineering*

In almost all human tissues and organs, adult stem cells or tissue stem cells are present in a unique location, the so-called stem cell niche or its equivalent, continuously replenishing functional differentiated cells. Those endogenous stem cells can be expanded for cell therapeutics using ex vivo cell culture or recalled for tissue repair in situ through cell trafficking and homing. In the aging process, inefficiency in the endogenous stem cell-mediated healing mechanism can emerge from a variety of impairments that accumulate in the processes of stem cell self-renewal, function, differentiation capacity, and trafficking through cell autonomous intrinsic pathways (such as epigenetic alterations) or systemic extrinsic pathways. This review examines the homeostasis of endogenous stem cells, particularly bone marrow stem cells, and their dysregulation in disease and aging and discusses possible intervention strategies. Several systemic pro-aging and rejuvenating factors, recognized in heterochronic parabiosis or premature aging progeroid animal models, are reviewed as possible anti-aging pharmaceutical targets from the perspective of a healthy environment for endogenous stem cells. A variety of epigenetic modifications and chromosome architectures are reviewed as an intrinsic cellular pathway for aging and senescence. A gradual increase in inflammatory burden during aging is also reviewed. Finally, the tissue repair and anti-aging effects of Substance-P, a peptide stimulating stem cell trafficking from the bone marrow and modifying the inflammatory response, are discussed as a future anti-aging target.
Adult Stem Cells ; Aging* ; Aging, Premature ; Bone Marrow ; Cell Culture Techniques ; Cell Self Renewal ; Epigenomics ; Hematopoietic Stem Cells ; Homeostasis* ; Humans ; Models, Animal ; Parabiosis ; Rejuvenation ; Stem Cell Niche ; Stem Cells*

Extracellular vesicles (EVs), a heterogenous group of membrane-bound particles, are virtually secreted by all cells and play important roles in cell-cell communication. Loaded with proteins, mRNAs, non-coding RNAs and membrane lipids from their donor cells, these vesicles participate in normal physiological and pathogenic processes. In addition, these subcellular vesicles are implicated in the progression of neurodegenerative disorders. Accumulating evidence suggests that intercellular communication via EVs is responsible for the propagation of key pathogenic proteins involved in the pathogenesis of amyotrophic lateral sclerosis, Parkinson's diseases, Alzheimer's diseases and other neurodegenerative disorders. For therapeutic perspective, EVs present advantage over other synthetic drug delivery systems or cell therapy; ability to cross biological barriers including blood brain barrier (BBB), ability to modulate inflammation and immune responses, stability and longer biodistribution with lack of tumorigenicity. In this review, we summarized the current state of EV research in central nervous system in terms of their values in diagnosis, disease pathology and therapeutic applications.
Amyotrophic Lateral Sclerosis ; Blood-Brain Barrier ; Cell- and Tissue-Based Therapy ; Central Nervous System ; Diagnosis ; Drug Delivery Systems ; Extracellular Vesicles* ; Humans ; Inflammation ; Membrane Lipids ; Neurodegenerative Diseases* ; Pathology ; RNA, Messenger ; RNA, Untranslated ; Tissue Donors

Liver failure is one of the main risks of death worldwide, and it originates from repetitive injuries and inflammations of liver tissues, which finally leads to the liver cirrhosis or cancer. Currently, liver transplantation is the only effective treatment for the liver diseases although it has a limitation due to donor scarcity. Alternatively, cell therapy to regenerate and reconstruct the damaged liver has been suggested to overcome the current limitation of liver disease cures. Several transplantable cell types could be utilized for recovering liver functions in injured liver, including bone marrow cells, mesenchymal stem cells, hematopoietic stem cells, macrophages, and stem cell-derived hepatocytes. Furthermore, paracrine effects of transplanted cells have been suggested as a new paradigm for liver disease cures, and this application would be a new strategy to cure liver failures. Therefore, here we reviewed the current status and challenges of therapy using stem cells for liver disease treatments.
Bone Marrow Cells ; Cell- and Tissue-Based Therapy ; Hematopoietic Stem Cells ; Hepatocytes ; Humans ; Inflammation ; Liver Cirrhosis ; Liver Diseases* ; Liver Failure ; Liver Regeneration ; Liver Transplantation ; Liver* ; Macrophages ; Mesenchymal Stromal Cells ; Stem Cell Transplantation ; Stem Cells* ; Tissue Donors

Recent advances in stem cell biology have dramatically increased the understanding of molecular and cellular mechanism of pluripotency and cell fate determination. Additionally, pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells, arose as essential resources for disease modeling and cellular therapeutics. Despite these advancements, the epigenetic dysregulation in pluripotency such as the imprinting status, and X chromosome dosage compensation, and its consequences on future utility of PSCs yet remain unresolved. In this review, we will focus on the X chromosome regulation in human PSCs (hPSCs). We will introduce the previous findings in the dosage compensation process on mouse model, and make comparison with those of human systems. Particularly, the X chromosome activation status of human preimplantation embryos, and the regulation of the active X chromosome by human specific lincRNA, X Active Coating Transcript (XACT), will be discussed. We will also discuss the recent findings on higher order X chromosome architecture, and abnormal X chromosome status in hPSCs.
Animals ; Biology* ; Blastocyst ; Chromosomes, Human, X* ; Compensation and Redress ; Embryonic Stem Cells ; Epigenomics ; Humans* ; Induced Pluripotent Stem Cells ; Mice ; Pluripotent Stem Cells ; Stem Cells* ; X Chromosome

No abstract available.
Regenerative Medicine* ; Stem Cell Research* ; Stem Cells*

Upper urinary tract-derived urine stem cells (USCs) are considered a valuable mesenchymal stem cell source for autologous cell therapy. However, the reported culture condition for USCs is not appropriate for large-quantity production, because cells can show limited replicativity, senescence, and undesirable differentiation during cultivation. These drawbacks led us to reconstitute a culture condition that mimics the natural stem cell niche. We selected extracellular matrix protein and oxygen tension to optimize the ex vivo expansion of USCs, and compared cell adhesion, proliferation, gene expression, chromosomal stability, differentiation capacity, immunity and safety. Culture on collagen type I (ColI) supported highly enhanced USC proliferation and retention of stem cell properties. In the oxygen tension analysis (with ColI), 5% O₂ hypoxia showed a higher cell proliferation rate, a greater proportion of cells in the S phase of the cell cycle, and normal stem cell properties compared to those observed in cells cultured under 20% O₂ normoxia. The established reconstituted condition (ColI/hypoxia, USCs(recon)) was compared to the control condition. The expanded USCs(recon) showed highly increased cell proliferation and colony forming ability, maintained transcription factors, chromosomal stability, and multi-lineage differentiation capacity (neuron, osteoblast, and adipocyte) compared to the control. In addition, USCs(recon) retained their immune-privileged potential and non-tumorigenicity with in vivo testing at week 8. Therefore, reconstituted condition allows for expanded uUSC cell preparations that are safe and useful for application in stem cell therapy.
Aging ; Anoxia ; Cell Adhesion ; Cell Cycle ; Cell Proliferation ; Cell- and Tissue-Based Therapy ; Chromosomal Instability ; Collagen Type I ; Extracellular Matrix ; Gene Expression ; Mesenchymal Stromal Cells ; Osteoblasts ; Oxygen ; S Phase ; Stem Cell Niche ; Stem Cells* ; Transcription Factors

Hydroxyapatite (HA) blocks as an alternative material for autogenous onlay bone grafts are regarded as an insufficient substitute for osseointegration of dental implant. In this study, we evaluated the effects of dog mesenchymal stromal cells (dMSCs) with or without bone morphogenetic protein-2 (BMP) on new peri-implant bone formation after HA block graft. In four mandibular bone defects (8×8×6 mm each) in five beagle dogs, dental implants were placed with HA block loaded with autogenous dMSCs with or without BMP-2. Animals were sacrificed at eight weeks, and bone healing was evaluated among four groups consisting of 1) HA alone as a control, 2) HA+dMSCs, 3) HA+BMP-2, and 4) HA+dMSCs+BMP-2. According to histomorphometric evaluation, the MSC+BMP-2 group and the BMP-2 group showed significantly higher bone-implant-contact (BIC) length than the MSC group, while there was no significant difference in new bone formation among the groups. According to micro-CT analysis, bone volume and bone mineral density were significantly higher in the MSC+BMP-2 group compared with the control group (p<0.01 and p<0.05, respectively). BIC was significantly higher in the MSC+BMP-2 group than both the control and MSC groups (p<0.01 and p<0.05, respectively). In conclusion, our results showed that bone regeneration at peri-implant bone defects grafted with HA blocks was significantly increased by dual delivery of MSCs and BMP-2. Conversely, HA blocks with MSC or BMP-2 alone did not allow for efficient peri-implant bone regeneration.
Animals ; Bone Density ; Bone Regeneration* ; Dental Implants ; Dogs ; Durapatite* ; Inlays ; Mesenchymal Stromal Cells* ; Osseointegration ; Osteogenesis ; Transplants*