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Insight into Microenvironment Remodeling in Pancreatic Endocrine Tissue Engineering: Biological and Biomaterial Approaches.

Maryam KAVIANI ; Negar AZARPIRA

Tissue Engineering and Regenerative Medicine.2016;13(5):475-484. doi:10.1007/10.1007/s13770-016-0014-1

The treatment of diabetes mellitus, as a chronic and complicated disease, is a valuable purpose. Islet transplantation can provide metabolic stability and insulin independence in type 1 diabetes patients. Diet and insulin therapy are only diabetes controllers and cannot remove all of the diabetes complications. Moreover, islet transplantation is more promising treatment than whole pancreas transplantation because of lesser invasive surgical procedure and morbidity and mortality. According to the importance of extracellular matrix for islet viability and function, microenvironment remodeling of pancreatic endocrine tissue can lead to more success in diabetes treatment by pancreatic islets. Production of bioengineered pancreas and remodeling of pancreas extracellular matrix provide essential microenvironment for re-vascularization, re-innervation and signaling cascades triggering. Therefore, islets show better viability and function in these conditions. Researchers conduct various scaffolds with different biomaterials for the improvement of islet viability, function and transplantation outcome. The attention to normal pancreas anatomy, embryology and histology is critical to understand the pancreatic Langerhans islets niche and finally to achieve efficient engineered structure. Therefore, in the present study, the status and components of the islets niche is mentioned and fundamental issues related to the tissue engineering of this structure is considered. The purpose of this review article is summarization of recent progress in the endocrine pancreas tissue engineering and biomaterials and biological aspects of it.
Biocompatible Materials ; Diabetes Complications ; Diabetes Mellitus ; Diet ; Embryology ; Extracellular Matrix ; Humans ; Insulin ; Islets of Langerhans ; Islets of Langerhans Transplantation ; Mortality ; Pancreas ; Pancreas Transplantation ; Tissue Engineering*

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The Therapeutic Potential of Stem Cells and Progenitor Cells for the Treatment of Parkinson's Disease.

Mooi Tiong LIAU ; Farahnaz AMINI ; Thamil Selvee RAMASAMY

Tissue Engineering and Regenerative Medicine.2016;13(5):455-464. doi:10.1007/s13770-016-9093-2

Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is usually seen in those above 50 years old. Current medical treatments only provide symptomatic relief but cannot cure the disease. There are claims that PD can be cured by stem cell transplant. The present study is aimed to assess the clinical potency and safety of stem cell in treating PD. A total of eleven articles were included for analysis, with four randomised control trials (RCTs), five non-RCTs and 2 follow up studies. All the four non-RCTs showed improvement of Unified Parkinson's Disease Rating Scale with no adverse events. However, results from RCTs showed no significant differences in the rating score among the transplant group and the Sham surgery group. The secondary analysis of one study showed a significant improvement of the rating score in those patients aged 60 and younger. Transplant group also associated with an overall higher incidence of adverse events. In conclusion, the RCTs and non-RCTs produced opposite results. When the studies were performed as non-RCTs in small number of patients, they showed promising result in the patients. It could say that currently the use of stem cell/progenitor cells in treating PD need much research despite having the implanted stem cell to be able to survive and integrated. The survival of implanted dopamine neurons in the striatum, however, does not indicate a success in correcting PD symptoms. Further investigations will shed light on the application and mechanism of action of stem cells in treating PD.
Cell- and Tissue-Based Therapy ; Dopaminergic Neurons ; Follow-Up Studies ; Humans ; Incidence ; Neurodegenerative Diseases ; Parkinson Disease* ; Stem Cell Transplantation ; Stem Cells*

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Microengineered Platforms for Co-Cultured Mesenchymal Stem Cells towards Vascularized Bone Tissue Engineering.

Hyeryeon PARK ; Dong Jin LIM ; Minhee SUNG ; Soo Hong LEE ; Dokyun NA ; Hansoo PARK

Tissue Engineering and Regenerative Medicine.2016;13(5):465-474. doi:10.1007/s13770-016-9080-7

Bone defects are common disease requiring thorough treatments since the bone is a complex vascularized tissue that is composed of multiple cell types embedded within an intricate extracellular matrix (ECM). For past decades, tissue engineering using cells, proteins, and scaffolds has been suggested as one of the promising approaches for effective bone regeneration. Recently, many researchers have been interested in designing effective platform for tissue regeneration by orchestrating factors involved in microenvironment around tissues. Among factors affecting bone formation, vascularization during bone development and after minor insults via endochondral and intramembranous ossification is especially critical for the long-term support for functional bone. In order to create vascularized bone constructs, the interactions between human mesenchymal stem cells (MSCs) and endothelial cells (ECs) have been investigated using both direct and indirect co-culture studies. Recently, various culture methods including micropatterning techniques, three dimensional scaffolds, and microfluidics have been developed to create micro-engineered platforms that mimic the nature of vascularized bone formation, leading to the creation of functional bone structures. This review focuses on MSCs co-cultured with endothelial cells and micro-engineered platforms to determine the underlying interplay between co-cultured MSCs and vascularized bone constructs, which is ultimately necessary for adequate regeneration of bone defects.
Bone and Bones* ; Bone Development ; Bone Regeneration ; Coculture Techniques ; Endothelial Cells ; Extracellular Matrix ; Humans ; Mesenchymal Stromal Cells* ; Microfluidics ; Osteogenesis ; Regeneration ; Stem Cells ; Tissue Engineering

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Efficient Biomaterials for Tissue Engineering of Female Reproductive Organs.

Amin TAMADON ; Kyu Hyung PARK ; Yoon Young KIM ; Byeong Cheol KANG ; Seung Yup KU

Tissue Engineering and Regenerative Medicine.2016;13(5):447-454. doi:10.1007/s13770-016-9107-0

Current investigations on the bioengineering of female reproductive tissues have created new hopes for the women suffering from reproductive organ failure including congenital anomaly of the female reproductive tract or serious injuries. There are many surgically restore forms that constitute congenital anomaly, however, to date, there is no treatment except surgical treatment of transplantation for patients who are suffering from anomaly or dysfunction organs like vagina and uterus. Restoring and maintaining the normal function of ovary and uterus require the establishment of biological substitutes that can cover the roles of structural support for cells and passage of secreting molecules. As in the case of constructing other functional organs, reproductive organ manufacturing also needs biological matrices which can provide an appropriate condition for attachment, growth, proliferation and signaling of various kinds of grafted cells. Among the organs, uterus needs special features such as plasticity due to their amazing changes in volume when they are in the state of pregnancy. Although numerous natural and synthetic biomaterials are still at the experimental stage, some biomaterials have already been evaluated their efficacy for the reconstruction of female reproductive tissues. In this review, all the biomaterials cited in recent literature that have ever been used and that have a potential for the tissue engineering of female reproductive organs were reviewed, especially focused on bioengineered ovary and uterus.
Biocompatible Materials* ; Bioengineering ; Female* ; Hope ; Humans ; Ovary ; Plastics ; Pregnancy ; Tissue Engineering* ; Transplants ; Uterus ; Vagina

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Behavior, PET and Histology in Novel Regimen of MPTP Marmoset Model of Parkinson's Disease for Long-Term Stem Cell Therapy.

Jun Won YUN ; Jae Bum AHN ; Euna KWON ; Jae Hun AHN ; Hyung Woo PARK ; Hwon HEO ; Jin Sung PARK ; Hyeonjin KIM ; Sun Ha PAEK ; Byeong Cheol KANG

Tissue Engineering and Regenerative Medicine.2016;13(1):100-109. doi:10.1007/s13770-015-0106-3

Stem cell technologies are particularly attractive in Parkinson's disease (PD) research although they occasionally need long-term treatment for anti-parkinsonian activity. Unfortunately, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) widely used as a model for PD has several limitations, including the risk of dose-dependent mortality and the difficulty of maintenance of PD symptoms during the whole experiment period. Therefore, we tested if our novel MPTP regimen protocol (2 mg/kg for 2 consecutive days and 1 mg/kg for next 3 consecutive days) can be maintained stable parkinsonism without mortality for long-term stem cell therapy. For this, we used small-bodied common marmoset monkeys (Callithrix jacchus) among several nonhuman primates showing high anatomical, functional, and behavioral similarities to humans. Along with no mortality, the behavioral changes involved in PD symptoms were maintained for 32 weeks. Also, the loss of jumping ability of the MPTP-treated marmosets in the Tower test was not recovered by 32 weeks. Positron emission tomography (PET) analysis revealed that remarkable decreases of bindings of ¹⁸F-FP-CIT were observed at the striatum of the brains of the marmosets received MPTP during the full period of the experiment for 32 weeks. In the substantia nigra of the marmosets, the loss of tyrosine hydroxylase (TH) immunoreactivity was also observed at 32 weeks following the MPTP treatment. In conclusion, our low-dose MPTP regimen protocol was found to be stable parkinsonism without mortality as evidenced by behavior, PET, and TH immunohistochemistry. This result will be useful for evaluation of possible long-term stem cell therapy for anti-parkinsonian activity.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine* ; Brain ; Callithrix* ; Haplorhini ; Humans ; Immunohistochemistry ; Models, Animal ; Mortality ; Parkinson Disease* ; Parkinsonian Disorders ; Positron-Emission Tomography ; Primates ; Stem Cells* ; Substantia Nigra ; Tyrosine 3-Monooxygenase

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STX0119 Ameliorates Arthritis in SKG Mice via Inhibiting T Helper 17.

Faisal HAYAT ; Seung Hoon LEE ; Eun Jung LEE ; Seok Jung KIM ; KyungAh JUNG ; Soon Kyu LEE ; Jeehee YOUN ; Jun Ki MIN ; Mi La CHO ; Dong Yun SHIN

Tissue Engineering and Regenerative Medicine.2016;13(1):91-99. doi:10.1007/s13770-016-9086-0

Rheumatoid arthritis (RA) is an autoimmune disease with chronic and excessive inflammation. Upregulation of interleukin (IL)-17 is involved in the pathogenesis of RA. STX0119 is a specific inhibitor of signal transducer and activator of transcription 3 (STAT3) as a potential target for the treatment of RA. STAT3 is a member of DNA-binding molecules that regulates the expression of proinflammatory cytokines involved in the pathogenesis of RA. The objective of this study was to determine whether STX0119 could inhibit STAT3 and IL-17. We demonstrated that STX0119 decreased T helper (Th) 17 differentiation and IL-17 expression in vitro. STX0119 also improved the severity of zymosan induced arthritis and reduced joint inflammation. STX0119 reduced the proliferation of Th17 and phosphorylated STAT3 expression while increasing Treg differentiation and phosphorylated STAT5 expression. Moreover, STX0119 decreased the expression of IL-6 and -17 but not IL-10. These findings suggest that STX0119 can be used to treat autoimmune RA through inhibiting the activation of STAT3.
Animals ; Arthritis* ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Cytokines ; In Vitro Techniques ; Inflammation ; Interleukin-10 ; Interleukin-17 ; Interleukin-6 ; Interleukins ; Joints ; Mice* ; STAT3 Transcription Factor ; Up-Regulation ; Zymosan

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Effect of Mesenchymal Stem Cells and Platelet-Derived Growth Factor on the Healing of Radiation Induced Ulcer in Rats.

Im Geon JIN ; Jin Ho KIM ; Hong Gyun WU ; Soon Jung HWANG

Tissue Engineering and Regenerative Medicine.2016;13(1):78-90. doi:10.1007/s13770-015-0055-x

Radiation-induced skin ulceration is a frequent complication of radiation therapy. This study investigated the effects of rat mesenchymal stem cells (rMSCs) and platelet-derived growth factor (PDGF) on the healing of radiation-induced soft tissue injury. Sprague-Dawley rats (n=17) were irradiated on the right and left buttocks with a single dose of 50 Gy. The right buttocks were administered with phosphate-buffered solution as a control. The left buttocks were administered with either rMSCs (2×10⁶ cells), PDGF (8 µg), or PDGF combined with rMSCs. Administration was done at three weeks after irradiation. Wound healing was analyzed by calculating the percentage of residual ulcerated skin area compared to the total irradiated area during the five week healing period after administration. Modified skin scores were also assessed. Finally, skin lesions were histologically evaluated. More than 40% of the irradiated skin area within the irradiated zone underwent ulceration within 16 days postirradiation, with peak ulceration exceeding 50% around three weeks post-irradiation. Administration of rMSCs or PDGF alone did not confer any significant healing effect. The combined rMSCs+PDGF treatment significantly reduced the wound size compared with the nontreated control up to two weeks postinjection. Regarding the histological examination, lesions administered with PDGF (either alone or mixed with rMSCs) resulted in a greater deposition of highly organized collagen fibers throughout the dermis layer, compared with the control. In conclusion, the combined administration of rMSCs and PDGF efficiently enhanced the healing of radiation-induced skin ulceration.
Animals ; Buttocks ; Collagen ; Dermis ; Mesenchymal Stromal Cells* ; Platelet-Derived Growth Factor* ; Rats* ; Rats, Sprague-Dawley ; Skin ; Skin Ulcer ; Soft Tissue Injuries ; Ulcer* ; Wound Healing ; Wounds and Injuries

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Histomorphometric Evaluation of Onlay Freeze-Dried Block Bone and Deproteinized Bovine Bone with Collagen in Rat.

Gyu Un JUNG ; Seong Jin HONG ; Ji Youn HONG ; Eun Kyoung PANG

Tissue Engineering and Regenerative Medicine.2016;13(1):70-77. doi:10.1007/s13770-016-9021-0

The aim of this study was to evaluate the effect of human freeze-dried bone block (FDBB) and deproteinized bovine bone with collagen (DBBC) on bone formation when applied as an onlay graft in rat calvariums. Thirty male Sprague-Dawley rats received collagen sponge (control), FDBB, or DBBC onlay grafts trimmed into 8-mm disks measuring 4-mm height. Each graft was secured onto the calvarium surface using horizontal mattress sutures. Rats in each group were killed at 2 (n=5) or 8 (n=5) weeks postoperatively for histologic and histomorphometric analysis. The total augmented area (mm²), new bone area (mm²), and bone density (%) were measured. The FDBB and DBBC groups showed significantly more new bone formation and bone density than the control group at 2 and 8 weeks. The increased new bone area was significantly greater in the FDBB group than in the DBBC group (p<0.05). The total augmented area was significantly higher in the FDBB and DBBC groups at 2 and 8 weeks than in the control group (p<0.05), and at 8 weeks, the area was significantly decreased in the DBBC group compared to that in the FDBB group and the area at 2 weeks (p<0.05). Within the limitations of the present study, we concluded that onlay FDBB and DBBC grafts caused new bone formation through an osteoconductive mechanism. In addition, compared to FDBB, DBBC had less capacity to form new bone and maintain the space.
Animals ; Bone Density ; Collagen* ; Humans ; Inlays* ; Male ; Osteogenesis ; Porifera ; Rats* ; Rats, Sprague-Dawley ; Skull ; Space Maintenance, Orthodontic ; Sutures ; Transplants

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Construction of a New T-Vector: Nickase (Nt.BspQI)-Generated T-Vector Bearing a Reddish-Orange Indicator Gene.

Ji Young CHOI ; Chulman JO ; Sangmee Ahn JO

Tissue Engineering and Regenerative Medicine.2016;13(1):66-69. doi:10.1007/s13770-015-0118-z

T-vectors are widely used for cloning the polymerase chain reaction (PCR) products. However, the low conversion efficiency of a plasmid into the linear T-vector usually results in non-recombinants. Here, we designed a new plasmid pNBQ-T to easily select the recombinant colonies harboring PCR products. pNBQ-T plasmid, which contains a DsRed indicator gene between two Nt.BspQI restriction cassettes, each of which contains palindromic sequences susceptible to Nt.BspQI nickase (5′-GCTCTTCT^GAAGAGC-3′) at each end. Thus, this plasmid can be easily converted into T-vectors by a nickase (quadruple nicking), which results in two double strand breaks with 3′-thymidine overhangs. DsRed indicator gene, which is inserted between the restriction sites, helps identifying the PCR recombinants. Using this pNBQ-T plasmid the insertion efficiency of a PCR product was examined. We successfully identified white colony of the recombinants with the inserted myostatin promoter gene: the cloning efficiency was 93%. Therefore, this simple method utilizing pNBQ-T plasmid will serve as a useful and efficient technique for preparation of home-made T-vectors.
Clone Cells ; Cloning, Organism ; Deoxyribonuclease I* ; Methods ; Myostatin ; Plasmids ; Polymerase Chain Reaction

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Extracellular Calcium-Binding Peptide-Modified Ceramics Stimulate Regeneration of Calvarial Bone Defects.

Ju Ang KIM ; Young Ae CHOI ; Hui Suk YUN ; Yong Chul BAE ; Hong In SHIN ; Eui Kyun PARK

Tissue Engineering and Regenerative Medicine.2016;13(1):57-65. doi:10.1007/s13770-015-9066-x

Secreted protein, acidic, cysteine-rich (SPARC)-related modular calcium binding 1 (SMOC1) has been implicated in the regulation of osteogenic differentiation of human bone marrow mesenchymal stem cells (BMSCs). In this study, we found that a peptide (16 amino acids in length), which is located in the extracellular calcium (EC) binding domain of SMOC1, stimulated osteogenic differentiation of human BMSCs in vitro and calvarial bone regeneration in vivo. Treatment of BMSCs with SMOC1-EC peptide significantly stimulated their mineralization in a dose-dependent manner without changing their rate of proliferation. The expression of osteogenic differentiation marker genes, including type 1 collagen and osteocalcin, also increased in a dose-dependent manner. To examine the effect of the SMOC1-EC peptide on bone formation in vivo, the peptide was covalently immobilized onto hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) particles. X-ray photoelectron spectroscopy analysis showed that the peptide was successfully immobilized onto the surface of HA/β-TCP. Implantation of the SMOC1-EC peptide-immobilized HA/β-TCP particles into mouse calvarial defects and subsequent analyses using microcomputed tomography and histology showed significant bone regeneration compared with that of calvarial defects implanted with unmodified HA/β-TCP particles. Collectively, our data suggest that a peptide derived from the EC domain of SMOC1 induces osteogenic differentiation of human BMSCs in vitro and efficiently enhances bone regeneration in vivo.
Amino Acids ; Animals ; Bone Marrow ; Bone Regeneration ; Calcium ; Ceramics* ; Collagen Type I ; Humans ; In Vitro Techniques ; Mesenchymal Stromal Cells ; Mice ; Miners ; Osteocalcin ; Osteogenesis ; Photoelectron Spectroscopy ; Regeneration* ; X-Ray Microtomography

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