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Correction to: Engineered M13 Nanofiber Accelerates Ischemic Neovascularization by Enhancing Endothelial Progenitor Cells

Jun Hee LEE ; Sung Wook KIM ; Seung Taek JI ; Yeon Ju KIM ; Woong Bi JANG ; Jin Woo OH ; Jaeho KIM ; So Young YOO ; Sang Hong BAEK ; Sang Mo KWON

Tissue Engineering and Regenerative Medicine.2018;15(1):129-129. doi:10.1007/10.1007/s13770-017-0109-3

There is a minor spelling error in the last of name of the 9th author in the originally published article.

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Correction to: Extracellular Vesicles in Neurodegenerative Diseases: A Double-Edged Sword

Ji Yong LEE ; Han Soo KIM

Tissue Engineering and Regenerative Medicine.2018;15(1):127-127. doi:10.1007/s13770-017-0110-x

Unfortunately, Acknowledgements section was missing in the originally published article.

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Correction to: New Advances in Human X Chromosome Status from a Developmental and Stem Cell Biology

Benjamin PATTERSON ; Yoshiaki TANAKA ; In Hyun PARK

Tissue Engineering and Regenerative Medicine.2018;15(1):125-125. doi:10.1007/s13770-017-0111-9

Unfortunately, Acknowledgements section was missing in the originally published article.

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Different Bone Healing Effects of Undifferentiated and Osteogenic Differentiated Mesenchymal Stromal Cell Sheets in Canine Radial Fracture Model

Yongseok YOON ; Imdad Ullah KHAN ; Kyeong Uk CHOI ; Taeseong JUNG ; Kwangrae JO ; Su Hyung LEE ; Wan Hee KIM ; Dae Yong KIM ; Oh Kyeong KWEON

Tissue Engineering and Regenerative Medicine.2018;15(1):115-124. doi:10.1007/s13770-017-0092-8

Cell sheets technology is being available for fracture healing. This study was performed to clarify bone healing mechanism of undifferentiated (UCS) and osteogenic (OCS) differentiated mesenchymal stromal cell (MSC) sheets in the fracture model of dogs. UCS and OCS were harvested at 10 days of culture. Transverse fractures at the radius of six beagle dogs were assigned into three groups (n = 4 in each group) i.e. UCS, OCS and control. The fractures were fixed with a 2.7 mm locking plate and six screws. Cell sheets were wrapped around the fracture site. Bones were harvested 8 weeks after operation, then scanned by micro-computed tomography (micro-CT) and analyzed histopathologically. The micro-CT revealed different aspects of bone regeneration among the groups. The percentages of external callus volume out of total bone volume in control, UCS, and OCS groups were 42.1, 13.0 and 4.9% (p < 0.05) respectively. However, the percentages of limbs having connectivity of gaps were 25, 12.5 and 75% respectively. In histopathological assessments, OCS group showed well organized and mature woven bone with peripheral cartilage at the fracture site, whereas control group showed cartilage formation without bone maturation or ossification at the fracture site. Meanwhile, fracture site was only filled with fibrous connective tissue without endochondral ossification and bone formation in UCS group. It was suggested that the MSC sheets reduced the quantity of external callus, and OCS induced the primary bone healing.
Animals ; Bone Regeneration ; Bony Callus ; Cartilage ; Connective Tissue ; Dogs ; Extremities ; Fracture Healing ; Mesenchymal Stromal Cells ; Osteogenesis ; Radius

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Osteochondral Regeneration with a Scaffold-Free Three-Dimensional Construct of Adipose Tissue-Derived Mesenchymal Stromal Cells in Pigs

Daiki MURATA ; Shizuka AKIEDA ; Kazuhiro MISUMI ; Koichi NAKAYAMA

Tissue Engineering and Regenerative Medicine.2018;15(1):101-113. doi:10.1007/s13770-017-0091-9

Osteochondral lesion is a major joint disease in humans. Therefore, this study was designed to investigate the regeneration of articular cartilage and subchondral bone, using three-dimensional constructs of autologous adipose tissue-derived mesenchymal stromal cells without any biocompatible scaffolds. Mesenchymal stromal cells were harvested by liposuction from seven pigs, isolated enzymatically, and expanded until construct creation. The pig models had two osteochondral defects (cylindrical defects with a diameter of 5.2 mm and a depth of 5 mm) in one of their patello-femoral grooves. A columnar structure consisting of approximately 770 spheroids of 5 × 10⁴ autologous mesenchymal stromal cells were implanted into one of the defects (implanted defect), while the other defect was not implanted (control). The defects were evaluated pathologically at 6 months (in three pigs) and 12 months (in five pigs) after implantation. At 6 months after surgery, histopathology revealed active endochondral ossification underneath the plump fibrocartilage in the implanted defects, but a deficiency of fibrocartilaginous coverage in the controls. At 12 months after surgery, the fibrocartilage was transforming into hyaline cartilage as thick as the surrounding normal cartilage and the subchondral bone was thickening in the implanted defects. The histological averages of the implanted sites were significantly higher than those in the control sites at both 6 and 12 months after surgery. The implantation of a scaffold-free three-dimensional construct of autologous mesenchymal stromal cells into an osteochondral defect can induce regeneration of hyaline cartilage and subchondral bone structures over a period of 12 months.
Adipose Tissue ; Cartilage ; Cartilage, Articular ; Fibrocartilage ; Humans ; Hyaline Cartilage ; Joint Diseases ; Lipectomy ; Mesenchymal Stromal Cells ; Regeneration ; Swine

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Implantation of Bone Marrow Stromal Cell Sheets Derived from Old Donors Supports Bone Tissue Formation

Manabu AKAHANE ; Takamasa SHIMIZU ; Yusuke INAGAKI ; Tsutomu KIRA ; Takuya EGAWA ; Akinori OKUDA ; Tadanobu ONISHI ; Tomoaki IMAMURA ; Yasuhito TANAKA

Tissue Engineering and Regenerative Medicine.2018;15(1):89-100. doi:10.1007/s13770-017-0088-4

The purpose of this study was to evaluate the osteogenesis ability of osteogenic matrix cell sheets (OMCS) derived from old donor cells. Bone marrow stromal cells (BMSC) were obtained from young (7-week-old) and old (1-year-old) Fischer344 rats donors and cultured with modified Eagle's medium (MEM group) alone or containing dexamethasone (Dex; 10 nM) and ascorbic acid phosphate (AscP; 0.28 mM) (Dex/AscP group). We prepared four in vitro experimental groups: (1) young MEM, (2) young Dex/AscP, (3) old MEM and (4) old Dex/AscP. Cell proliferation and osteogenic marker mRNA expression levels were evaluated in vitro. To assess bone formation in vivo, the cells of each group were combined with beta tricalcium phosphate (TCP) disks followed by implantation in recipient rats. The in vitro study showed significant differences in the mRNA expression of osteocalcin, ALP, and BMP2 between MEM and Dex/AscP groups. Bone formation following implantation was observed upon histological analyses of all groups. TCP combined with OMCS (OMCS/TCP group) resulted in enhanced bone formation compared to that following combination with BMSC (BMSC/TCP). The osteocalcin content of the OMCS/TCP group 4 weeks after implantation was significantly higher than that in the BMSC/TCP construct for both young and old donors. The present study clearly indicated that OMCS could be generated from BMSCs of old as well as young donors using a mechanical retrieval method. Thus, through its usage of OMCS, this method may represent a potentially effective therapeutic option for cell-based therapy in elderly patients.
Aged ; Animals ; Ascorbic Acid ; Bone and Bones ; Bone Marrow ; Cell Proliferation ; Dexamethasone ; Humans ; In Vitro Techniques ; Mesenchymal Stromal Cells ; Methods ; Osteocalcin ; Osteogenesis ; Rats ; RNA, Messenger ; Tissue Donors

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Mesenchymal Stromal Cells from the Maternal Segment of Human Umbilical Cord is Ideal for Bone Regeneration in Allogenic Setting

Jezamine LIM ; Zainul Rashid Mohamad RAZI ; Jia Xian LAW ; Azmawati Mohammed NAWI ; Ruszymah Binti Haji IDRUS ; Tan Geok CHIN ; Muaatamarulain MUSTANGIN ; Min Hwei NG

Tissue Engineering and Regenerative Medicine.2018;15(1):75-87. doi:10.1007/s13770-017-0086-6

Umbilical cord (UC) is a discarded product from the operating theatre and a ready source of mesenchymal stromal cells (MSCs). MSCs from UC express both embryonic and adult mesenchymal stem cell markers and are known to be hypoimmunogenic and non-tumorigenic and thus suitable for allogeneic cell transplantation. Our study aimed to determine the degree of immunotolerance and bone-forming capacity of osteodifferentiated human Wharton's jelly-derived mesenchymal stromal cells (hWJ-MSCs) from different segments of UC in an allogenic setting. UCs were obtained from healthy donors delivering a full-term infant by elective Caesarean section. hWJ-MSCs were isolated from 3 cm length segment from the maternal and foetal ends of UCs. Three-dimensional fibrin constructs were formed and implanted intramuscularly into immunocompetent mice. The mice were implanted with 1) fibrin construct with maternal hWJ-MSCs, 2) fibrin construct with foetal hWJ-MSCs, or 3) fibrin without cells; the control group received sham surgery. After 1 month, the lymphoid organs were analysed to determine the degree of immune rejection and bone constructs were analysed to determine the amount of bone formed. A pronounced immune reaction was noted in the fibrin group. The maternal segment constructs demonstrated greater osteogenesis than the foetal segment constructs. Both maternal and foetal segment constructs caused minimal immune reaction and thus appear to be safe for allogeneic bone transplant. The suppression of inflammation may be a result of increased anti-inflammatory cytokine production mediated by the hWJ-MSC. In summary, this study demonstrates the feasibility of using bone constructs derived from hWJ-MSCs in an allogenic setting.
Adult ; Animals ; Bone Regeneration ; Cell Transplantation ; Cesarean Section ; Female ; Fibrin ; Humans ; Infant ; Inflammation ; Mesenchymal Stromal Cells ; Mice ; Osteogenesis ; Pregnancy ; Tissue Donors ; Tissue Engineering ; Transplants ; Umbilical Cord ; Wharton Jelly

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Substance-P Ameliorates Dextran Sodium Sulfate-Induced Intestinal Damage by Preserving Tissue Barrier Function

Dae Yeon HWANG ; Suna KIM ; Hyun Sook HONG

Tissue Engineering and Regenerative Medicine.2018;15(1):63-73. doi:10.1007/s13770-017-0085-7

Intestinal inflammation alters immune responses in the mucosa and destroys colon architecture, leading to serious diseases such as inflammatory bowel disease. Thus, the modulation of intestinal integrity and immune responses in IBD can be the critical factor to be considered to reduce the severity of damages. Substance-P (SP), endogenous peptide to be involved in cell proliferation, migration and immune modulation, can exert the therapeutic effect on diverse diseases including cornea damage, rheumatoid arthritis and diabetic complications. SP was found to elevate expression of junctional molecule. Considering the function of SP reported previously, it was inferred that SP is capable of exert the beneficial effect of SP on intestinal diseases by controlling intestinal structure as well as immune responses. In this study, we explored the therapeutic effect of SP on dextran sodium sulfate-induced intestine damage by injecting SP. The effects of SP were evaluated by analyzing crypt structures, proliferating cell pool and infiltration of immune cells. DSS treatment provoked abnormal immune response and disruption of intestine epithelial barrier. However, co-treatment of SP obviously blocked the development of intestinal damages by declining inflammatory responses and sustaining intestinal structure more intact. The treatment of SP to chronic damages also promoted intestinal regeneration by preserving the integrity of colon tissue. Moreover, DSS-induced reduction of epithelial junctional molecule was obviously inhibited by SP treatment in vitro. Taken together, our data indicate that SP can reduce intestinal damages, possibly by modulating barrier structure and immune response. Our results propose SP as candidate therapeutics in intestinal damages.
Arthritis, Rheumatoid ; Cell Proliferation ; Colon ; Cornea ; Dextrans ; Diabetes Complications ; In Vitro Techniques ; Inflammation ; Inflammatory Bowel Diseases ; Intestinal Diseases ; Intestines ; Mucous Membrane ; Regeneration ; Sodium ; Tight Junctions

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Adipose Stem Cells with Conditioned Media for Treatment of Acne Vulgaris Scar

Xing SHAN ; Jong Hyeon CHOI ; Ki Joo KIM ; Yoon Jae LEE ; Yeon Hee RYU ; Su Jin LEE ; Suk Ho MOON ; Jong Won RHIE

Tissue Engineering and Regenerative Medicine.2018;15(1):49-61. doi:10.1007/s13770-017-0105-7

This study was to investigate the effect of subcutaneous injection of the adipose stem cells (ASCs) with conditioned media (CM) in the treatment of acne vulgaris scar. We used Adult male New Zealand white rabbit ears as an animal model and induced acne formation by Kignman method. Adipose tissue was isolated and harvested from the scapula of rabbits, and ASCs were cultured and expanded until passage 1. There have four groups in our experiment, include phosphate buffered saline (PBS), ASCs with PBS (ASC + PBS), CM, and ASCs with CM (ASC + CM) group. This solution of 0.6 ml injected to subcutaneous in each group. ASC + PBS and ASC + CM groups were containing ASCs of 5.0 × 106 cells/ml. We analyzed the treatment of 4 groups to scar tissue after 2 and 4 weeks by hematoxylin and eosin stain, immunohistochemistry, and RNA expression level of tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), and matrix metalloproteinase-2 (MMP-2). Also, the expression of keratin 16 (K16) was detected by western blot analysis. H&E stain showed that infiltration of inflammation cells was significantly reduced at 2 and 4 weeks, as well as re-epithelialization was improved in the ASC + CM group. The ASC + CM gourp was reduced both expression levels of TNF-α, IL-1α, and MMP-2 and K16 protein level. In conclusion, the ASCs with CM has a significant curative effect on acne vulgaris scar, more to the point, the CM has a key role on treatment. It could be applied to a therapeutic approach to regenerate to treat acne vulgaris scar.
Acne Vulgaris ; Adipose Tissue ; Adult ; Blotting, Western ; Cicatrix ; Culture Media, Conditioned ; Ear ; Eosine Yellowish-(YS) ; Hematoxylin ; Humans ; Immunohistochemistry ; Inflammation ; Injections, Subcutaneous ; Keratin-16 ; Male ; Matrix Metalloproteinase 2 ; Methods ; Models, Animal ; Necrosis ; New Zealand ; Rabbits ; Re-Epithelialization ; RNA ; Scapula ; Stem Cells

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Non-contact Coculture Reveals a Comprehensive Response of Chondrocytes Induced by Mesenchymal Stem Cells Through Trophic Secretion

Lei XU ; Yuxi WU ; Yanli LIU ; Yan ZHOU ; Zhaoyang YE ; Wen Song TAN

Tissue Engineering and Regenerative Medicine.2018;15(1):37-48. doi:10.1007/s13770-017-0084-8

Coculture between mesenchymal stem cells (MSCs) and chondrocytes has significant implications in cartilage regeneration. However, a conclusive understanding remains elusive. Previously, we reported that rabbit bone marrow-derived MSCs (rbBMSCs) could downregulate the differentiated phenotype of rabbit articular chondrocytes (rbACs) in a non-contact coculture system for the first time. In the present study, a systemic investigation was performed to understand the biological characteristics of chondrocytes in coculture with MSCs. Firstly, cells (MSCs and chondrocytes) from different origins were cocultured in transwell system. Different chondrocytes, when cocultured with different MSCs respectively, consistently demonstrated stimulated proliferation, transformed morphology and declined glycosaminoglycan secretion of chondrocytes. Next, cell surface molecules and the global gene expression of rbACs were characterized. It was found that cocultured rbACs showed a distinct surface molecule profile and global gene expression compared to both dedifferentiated rbACs and rbBMSCs. In the end, cocultured rbACs were passaged and induced to undergo the chondrogenic redifferentiation. Better growth and chondrogenesis ability were confirmed compared with control cells without coculture. Together, chondrocytes display comprehensive changes in coculture with MSCs and the cocultured rbACs are beneficial for cartilage repair.
Cartilage ; Chondrocytes ; Chondrogenesis ; Coculture Techniques ; Gene Expression ; Mesenchymal Stromal Cells ; Phenotype ; Population Characteristics ; Regeneration

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