1.Tissue engineering and regenerative medicine approaches in colorectal surgery
Bigyan B. MAINALI ; James J. YOO ; Mitchell R. LADD
Annals of Coloproctology 2024;40(4):336-349
Tissue engineering and regenerative medicine (TERM) is an emerging field that has provided new therapeutic opportunities by delivering innovative solutions. The development of nontraditional therapies for previously unsolvable diseases and conditions has brought hope and excitement to countless individuals globally. Many regenerative medicine therapies have been developed and delivered to patients clinically. The technology platforms developed in regenerative medicine have been expanded to various medical areas; however, their applications in colorectal surgery remain limited. Applying TERM technologies to engineer biological tissue and organ substitutes may address the current therapeutic challenges and overcome some complications in colorectal surgery, such as inflammatory bowel diseases, short bowel syndrome, and diseases of motility and neuromuscular function. This review provides a comprehensive overview of TERM applications in colorectal surgery, highlighting the current state of the art, including preclinical and clinical studies, current challenges, and future perspectives. This article synthesizes the latest findings, providing a valuable resource for clinicians and researchers aiming to integrate TERM into colorectal surgical practice.
2.Application of Cartilage Extracellular Matrix to Enhance Therapeutic Efficacy of Methotrexate
Jeong-Woo SEO ; Sung-Han JO ; Seon-Hwa KIM ; Byeong-Hoon CHOI ; Hongsik CHO ; James J. YOO ; Sang-Hyug PARK
Tissue Engineering and Regenerative Medicine 2024;21(2):209-221
BACKGROUND:
Rheumatoid arthritis (RA) is characterized by chronic inflammation and joint damage. Methotrexate (MTX), a commonly used disease-modifying anti-rheumatic drug (DMARD) used in RA treatment. However, the continued use of DMARDs can cause adverse effects and result in limited therapeutic efficacy. Cartilage extracellular matrix (CECM) has anti-inflammatory and anti-vascular effects and promotes stem cell migration, adhesion, and differentiation into cartilage cells.
METHODS:
CECM was assessed the dsDNA, glycosaminoglycan, collagen contents and FT-IR spectrum of CECM.Furthermore, we determined the effects of CECM and MTX on cytocompatibility in the SW 982 cells and RAW 264.7 cells. The anti-inflammatory effects of CECM and MTX were assessed using macrophage cells. Finally, we examined the in vivo effects of CECM in combination with MTX on anti-inflammation control and cartilage degradation in collageninduced arthritis model. Anti-inflammation control and cartilage degradation were assessed by measuring the serum levels of RA-related cytokines and histology.
RESULTS:
CECM in combination with MTX had no effect on SW 982, effectively suppressing only RAW 264.7 activity.Moreover, anti-inflammatory effects were enhanced when low-dose MTX was combined with CECM. In a collageninduced arthritis model, low-dose MTX combined with CECM remarkably reduced RA-related and pro-inflammatory cytokine levels in the blood. Additionally, low-dose MTX combined with CECM exerted the best cartilage-preservation effects compared to those observed in the other therapy groups.
CONCLUSION
Using CECM as an adjuvant in RA treatment can augment the therapeutic effects of MTX, reduce existing drug adverse effects, and promote joint tissue regeneration.
3.Synovium-Derived Mesenchymal Stem Cell-Based Scaffold-Free Fibrocartilage Engineering for Bone–Tendon Interface Healing in an Anterior Cruciate Ligament Reconstruction Model
Sujin NOH ; Sang Jin LEE ; James J. YOO ; Yong Jun JIN ; Hee-Woong YUN ; Byoung-Hyun MIN ; Jae-Young PARK ; Do Young PARK
Tissue Engineering and Regenerative Medicine 2024;21(2):341-351
BACKGROUND:
Current tendon and ligament reconstruction surgeries rely on scar tissue healing which differs from native bone-to-tendon interface (BTI) tissue. We aimed to engineer Synovium-derived mesenchymal stem cells (Sy-MSCs) based scaffold-free fibrocartilage constructs and investigate in vivo bone–tendon interface (BTI) healing efficacy in a rat anterior cruciate ligament (ACL) reconstruction model.
METHODS:
Sy-MSCs were isolated from knee joint of rats. Scaffold-free sy-MSC constructs were fabricated and cultured in differentiation media including TGF-b-only, CTGF-only, and TGF-b + CTGF. Collagenase treatment on tendon grafts was optimized to improve cell-to-graft integration. The effects of fibrocartilage differentiation and collagenase treatment on BTI integration was assessed by conducting histological staining, cell adhesion assay, and tensile testing. Finally, histological and biomechanical analyses were used to evaluate in vivo efficacy of fibrocartilage construct in a rat ACL reconstruction model.
RESULTS:
Fibrocartilage-like features were observed with in the scaffold-free sy-MSC constructs when applying TGF-band CTGF concurrently. Fifteen minutes collagenase treatment increased cellular attachment 1.9-fold compared to the Control group without affecting tensile strength. The failure stress was highest in the Col + D + group (22.494 ± 13.74 Kpa) compared to other groups at integration analysis in vitro. The ACL Recon + FC group exhibited a significant 88% increase in estimated stiffness (p = 0.0102) compared to the ACL Recon group at the 4-week postoperative period.
CONCLUSION
Scaffold-free, fibrocartilage engineering together with tendon collagenase treatment enhanced fibrocartilaginous BTI healing in ACL reconstruction.
4.Clinical and Safety Outcomes of Endovascular Therapy 6 to 24 Hours After Large Vessel Occlusion Ischemic Stroke With Tandem Lesions
Milagros GALECIO-CASTILLO ; Mudassir FAROOQUI ; Ameer E. HASSAN ; Mouhammad A. JUMAA ; Afshin A. DIVANI ; Marc RIBO ; Michael ABRAHAM ; Nils H. PETERSEN ; Johanna T. FIFI ; Waldo R. GUERRERO ; Amer M. MALIK ; James E. SIEGLER ; Thanh N. NGUYEN ; Sunil SHETH ; Albert J. YOO ; Guillermo LINARES ; Nazli JANJUA ; Darko QUISPE-OROZCO ; Wondwossen TEKLE ; Syed F. ZAIDI ; Sara Y. SABBAGH ; Marta OLIVÉ-GADEA ; Tiffany BARKLEY ; Reade De LEACY ; Kenyon W. SPRANKLE ; Mohamad ABDALKADER ; Sergio SALAZAR-MARIONI ; Jazba SOOMRO ; Weston GORDON ; Charoskhon TURABOVA ; Juan VIVANCO-SUAREZ ; Aaron RODRIGUEZ-CALIENES ; Maxim MOKIN ; Dileep R. YAVAGAL ; Tudor JOVIN ; Santiago ORTEGA-GUTIERREZ
Journal of Stroke 2023;25(3):378-387
Background:
and Purpose Effect of endovascular therapy (EVT) in acute large vessel occlusion (LVO) patients with tandem lesions (TLs) within 6–24 hours after last known well (LKW) remains unclear. We evaluated the clinical and safety outcomes among TL-LVO patients treated within 6–24 hours.
Methods:
This multicenter cohort was divided into two groups, based on LKW to puncture time: early window (<6 hours), and late window (6–24 hours). Primary clinical and safety outcomes were 90-day functional independence measured by the modified Rankin Scale (mRS: 0–2) and symptomatic intracranial hemorrhage (sICH). Secondary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction score ≥2b), first-pass effect, early neurological improvement, ordinal mRS, and in-hospital and 90-day mortality.
Results:
Of 579 patients (median age 68, 32.1% females), 268 (46.3%) were treated in the late window and 311 (53.7%) in the early window. Late window group had lower median National Institutes of Health Stroke Scale score at admission, Alberta Stroke Program Early Computed Tomography Score, rates of intravenous thrombolysis, and higher rates for perfusion imaging. After adjusting for confounders, the odds of 90-day mRS 0–2 (47.7% vs. 45.0%, adjusted odds ratio [aOR] 0.71, 95% confidence interval [CI] 0.49–1.02), favorable shift in mRS (aOR 0.88, 95% CI 0.44–1.76), and sICH (3.7% vs. 5.2%, aOR 0.56, 95% CI 0.20–1.56) were similar in both groups. There was no difference in secondary outcomes. Increased time from LKW to puncture did not predicted the probability of 90-day mRS 0–2 (aOR 0.99, 95% CI 0.96–1.01, for each hour delay) among patients presenting <24 hours.
Conclusion
EVT for acute TL-LVO treated within 6–24 hours after LKW was associated with similar rates of clinical and safety outcomes, compared to patients treated within 6 hours.
5.Microfluidic Systems for Assisted Reproductive Technologies: Advantages and Potential Applications
Russel C. SEQUEIRA ; Tracy CRISWELL ; Anthony ATALA ; James J. YOO
Tissue Engineering and Regenerative Medicine 2020;17(6):787-800
Microfluidic technologies have emerged as a powerful tool that can closely replicate the in-vivo physiological conditions of organ systems. Assisted reproductive technology (ART), while being able to achieve successful outcomes, still faces challenges related to technical error, efficiency, cost, and monitoring/assessment. In this review, we provide a brief overview of the uses of microfluidic devices in the culture, maintenance and study of ovarian follicle development for experimental and therapeutic applications. We discuss existing microfluidic platforms for oocyte and sperm selection and maintenance, facilitation of fertilization by in-vitro fertilization/intracytoplastimc sperm injection, and monitoring, selection and maintenance of resulting embryos. Furthermore, we discuss the possibility of future integration of these technologies onto a single platform and the limitations facing the development of these systems. In spite of these challenges, we envision that microfluidic systems will likely evolve and inevitably revolutionize both fundamental, reproductive physiology/toxicology research as well as clinically applicable ART.
7.Microfluidic Systems for Assisted Reproductive Technologies: Advantages and Potential Applications
Russel C. SEQUEIRA ; Tracy CRISWELL ; Anthony ATALA ; James J. YOO
Tissue Engineering and Regenerative Medicine 2020;17(6):787-800
Microfluidic technologies have emerged as a powerful tool that can closely replicate the in-vivo physiological conditions of organ systems. Assisted reproductive technology (ART), while being able to achieve successful outcomes, still faces challenges related to technical error, efficiency, cost, and monitoring/assessment. In this review, we provide a brief overview of the uses of microfluidic devices in the culture, maintenance and study of ovarian follicle development for experimental and therapeutic applications. We discuss existing microfluidic platforms for oocyte and sperm selection and maintenance, facilitation of fertilization by in-vitro fertilization/intracytoplastimc sperm injection, and monitoring, selection and maintenance of resulting embryos. Furthermore, we discuss the possibility of future integration of these technologies onto a single platform and the limitations facing the development of these systems. In spite of these challenges, we envision that microfluidic systems will likely evolve and inevitably revolutionize both fundamental, reproductive physiology/toxicology research as well as clinically applicable ART.
9.State-of-the-Art Strategies for the Vascularization of Three-Dimensional Engineered Organs
Sangil MIN ; In Kap KO ; James J YOO
Vascular Specialist International 2019;35(2):77-89
Engineering three-dimensional (3D) implantable tissue constructs is a promising strategy for replacing damaged or diseased tissues and organs with functional replacements. However, the efficient vascularization of new 3D organs is a major scientific and technical challenge since large tissue constructs or organs require a constant blood supply to survive in vivo. Current approaches to solving this problem generally fall into the following three major categories: (a) cell-based, (b) angiogenic factor-based, and (c) scaffold-based. In this review, we summarize state-of-the-art technologies that are used to develop complex, stable, and functional vasculature for engineered 3D tissue constructs and organs; additionally, we have suggested directions for future research.
Bioengineering
;
Tissue Scaffolds
10.Cell-derived Secretome for the Treatment of Renal Disease
Michael W. KIM ; In Kap KO ; Anthony ATALA ; James J. YOO
Childhood Kidney Diseases 2019;23(2):67-76
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 cellbased 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.
Dialysis
;
Global Health
;
Kidney
;
Kidney Diseases
;
Kidney Failure, Chronic
;
Kidney Transplantation
;
Regenerative Medicine
;
Renal Dialysis
;
Renal Insufficiency

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