BACKGROUND: Mesenchymal stem cells (MSCs) derived from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC) exhibit therapeutic potential in regenerative medicine. However, their properties, including transcriptomic profiles, vary based on tissue origin, passage stage, and isolation method, complicating their clinical standardization.Addressing these unresolved differences requires comprehensive approaches, such as RNA sequencing, to analyze transcriptomic profiles in detail. METHODS: In this study, RNA-seq was employed to analyze MSC transcriptomes from BM, AD, and UC tissues. UC MSCs were isolated using enzymatic digestion or the Minimal Cube Explant (MCE) method (smumf cells), and transcriptomes of early (P3–4) and late (P10) passages of smumf cells were compared. Differentially expressed genes (DEGs) were identified, followed by transcription factor (TF) and pathway analyses. RESULTS: Fetal MSCs (UC and smumf cells) exhibited distinct transcriptomic profiles compared to adult MSCs (BM and AD), with 2,208 upregulated and 2,594 downregulated DEGs. Key transcription factors, such as E2F1 and NF-jB1, and pathways, including glycolysis, cholesterol biosynthesis, and TNF-a signaling, were enriched in fetal MSCs. smumf cells demonstrated transcriptomic stability between early and late passages, with only 12 DEGs identified. Additionally, smumf cells showed enhanced innate immune responses and cholesterol metabolism compared to enzymatically isolated UC MSCs. CONCLUSION This study provides a comprehensive transcriptomic comparison of MSCs, highlighting the superior transcriptional stability, immunomodulatory capacity, and metabolic flexibility of fetal MSCs, particularly smumf cells. These findings underscore their potential as a reliable cell source for therapeutic applications and encourage further exploration of their clinical application.

Background: This study aimed to investigate changes in gene expression related to matrix synthesis in individuals with fullthickness rotator cuff tears (RCTs) and normal tendon tissues. The study also aimed to examine the differences in gene expression according to 4 distinct tear sizes. Methods: A total of 12 patients with full-thickness RCTs were included in the study, all of whom underwent arthroscopic rotator cuff repair. The RCTs were stratified by size into small, medium, large, and massive. Tendon samples were harvested from the midpoint between the lateral end of the torn tendon and the musculotendinous junction. Subsequent analysis of the tissue samples revealed the mRNA expression levels of 11 collagen types, 6 proteoglycans, and 8 glycoproteins through real-time polymerase chain reaction techniques. For control purposes, supraspinatus tendon tissue was sourced from 3 patients who had proximal humerus fractures but did not present with RCTs. Results: Among the 11 collagens and 14 non-collagenous protein (NCP) genes examined in this study, COL3A1 and COL10A1 showed a significant increase, whereas COL4A1 and COL14A1 showed a tendency to decrease compared to those in the normal group. ACAN significantly increased by 8.92-fold (p < 0.001) compared to that in the normal group, whereas DCN and LUM showed a tendency to decrease. FN1 and TNC increased significantly by 3.47-fold (p = 0.003) and 5.38-fold (p = 0.005), respectively, and the genes ELN, LAMA2, and THBS1 were all significantly reduced compared to those in the normal group. In the NCPs, almost all the genes with increased expression levels had the highest level in small size RCTs, and gene expression decreased as the size increased. The 3 proteoglycans (ACAN, BGN, and FMOD) showed the highest levels of expression in small size RCTs compared to those in the normal group, and 5 glycoproteins (COMP, FBN1, FN1, HAPLN1, and TNC) also showed the highest expression in small size RCTs. Conclusions We confirmed that most of the detected extracellular matrix gene expression changes were related to the size of the full-thickness RCTs. In NCPs, gene expression was increased in small-size tears, and gene expression levels were significantly reduced when the size increased.

Background: To investigate the feasibility of the antegrade supraspinatus advancement (ASSA), which could be executed entirely arthroscopically without requiring a medial incision; to evaluate the impact of the ASSA on the lateral excursion of the torn end of the supraspinatus in retracted irreducible rotator cuff tears (RIRCTs); and to assess the safety and efficacy of arthroscopic rotator cuff repair with the ASSA. Methods: A total of 57 patients with RIRCTs who underwent the ASSA and were followed up for at least a year with magnetic resonance imaging (MRI) were included. The RIRCT was defined as the lateral excursion grade C (coverage less than the medial half of the greater tuberosity) or D (exposure of the glenohumeral joint). Clinical outcomes assessed nerve injury, pain, range of motion, strength, functional scores, and overall satisfaction and function. Structural outcomes evaluated the retear rate, fatty infiltration, and muscle atrophy of the rotator cuff muscles. The baseline for these structural measurements was time-zero MRIs. Results: The ASSA was feasibly performed all arthroscopically without a medial incision. There was no suprascapular nerve injury during the follow-up. The ASSA increased lateral excursion of the torn end in 86% of the patients from C or D to A or B. The ASSA significantly reduced pain and improved function of the shoulder at the final follow-up. All 11 patients who had had pseudoparalysis prior to repair regained the ability to raise their arm. The retear rate after the ASSA was 18.4%. Conclusions This study demonstrated that the ASSA can be safely and effectively performed all arthroscopically, significantly increasing the lateral excursion of the supraspinatus, thereby ensuring successful rotator cuff repair. This leads to a superior quality of repair, which consequently results in better clinical and structural outcomes, including the reversal of pseudoparalysis.

Background: This study aimed to investigate changes in gene expression related to matrix synthesis in individuals with fullthickness rotator cuff tears (RCTs) and normal tendon tissues. The study also aimed to examine the differences in gene expression according to 4 distinct tear sizes. Methods: A total of 12 patients with full-thickness RCTs were included in the study, all of whom underwent arthroscopic rotator cuff repair. The RCTs were stratified by size into small, medium, large, and massive. Tendon samples were harvested from the midpoint between the lateral end of the torn tendon and the musculotendinous junction. Subsequent analysis of the tissue samples revealed the mRNA expression levels of 11 collagen types, 6 proteoglycans, and 8 glycoproteins through real-time polymerase chain reaction techniques. For control purposes, supraspinatus tendon tissue was sourced from 3 patients who had proximal humerus fractures but did not present with RCTs. Results: Among the 11 collagens and 14 non-collagenous protein (NCP) genes examined in this study, COL3A1 and COL10A1 showed a significant increase, whereas COL4A1 and COL14A1 showed a tendency to decrease compared to those in the normal group. ACAN significantly increased by 8.92-fold (p < 0.001) compared to that in the normal group, whereas DCN and LUM showed a tendency to decrease. FN1 and TNC increased significantly by 3.47-fold (p = 0.003) and 5.38-fold (p = 0.005), respectively, and the genes ELN, LAMA2, and THBS1 were all significantly reduced compared to those in the normal group. In the NCPs, almost all the genes with increased expression levels had the highest level in small size RCTs, and gene expression decreased as the size increased. The 3 proteoglycans (ACAN, BGN, and FMOD) showed the highest levels of expression in small size RCTs compared to those in the normal group, and 5 glycoproteins (COMP, FBN1, FN1, HAPLN1, and TNC) also showed the highest expression in small size RCTs. Conclusions We confirmed that most of the detected extracellular matrix gene expression changes were related to the size of the full-thickness RCTs. In NCPs, gene expression was increased in small-size tears, and gene expression levels were significantly reduced when the size increased.

Background: To investigate the feasibility of the antegrade supraspinatus advancement (ASSA), which could be executed entirely arthroscopically without requiring a medial incision; to evaluate the impact of the ASSA on the lateral excursion of the torn end of the supraspinatus in retracted irreducible rotator cuff tears (RIRCTs); and to assess the safety and efficacy of arthroscopic rotator cuff repair with the ASSA. Methods: A total of 57 patients with RIRCTs who underwent the ASSA and were followed up for at least a year with magnetic resonance imaging (MRI) were included. The RIRCT was defined as the lateral excursion grade C (coverage less than the medial half of the greater tuberosity) or D (exposure of the glenohumeral joint). Clinical outcomes assessed nerve injury, pain, range of motion, strength, functional scores, and overall satisfaction and function. Structural outcomes evaluated the retear rate, fatty infiltration, and muscle atrophy of the rotator cuff muscles. The baseline for these structural measurements was time-zero MRIs. Results: The ASSA was feasibly performed all arthroscopically without a medial incision. There was no suprascapular nerve injury during the follow-up. The ASSA increased lateral excursion of the torn end in 86% of the patients from C or D to A or B. The ASSA significantly reduced pain and improved function of the shoulder at the final follow-up. All 11 patients who had had pseudoparalysis prior to repair regained the ability to raise their arm. The retear rate after the ASSA was 18.4%. Conclusions This study demonstrated that the ASSA can be safely and effectively performed all arthroscopically, significantly increasing the lateral excursion of the supraspinatus, thereby ensuring successful rotator cuff repair. This leads to a superior quality of repair, which consequently results in better clinical and structural outcomes, including the reversal of pseudoparalysis.

Background: This study aimed to investigate changes in gene expression related to matrix synthesis in individuals with fullthickness rotator cuff tears (RCTs) and normal tendon tissues. The study also aimed to examine the differences in gene expression according to 4 distinct tear sizes. Methods: A total of 12 patients with full-thickness RCTs were included in the study, all of whom underwent arthroscopic rotator cuff repair. The RCTs were stratified by size into small, medium, large, and massive. Tendon samples were harvested from the midpoint between the lateral end of the torn tendon and the musculotendinous junction. Subsequent analysis of the tissue samples revealed the mRNA expression levels of 11 collagen types, 6 proteoglycans, and 8 glycoproteins through real-time polymerase chain reaction techniques. For control purposes, supraspinatus tendon tissue was sourced from 3 patients who had proximal humerus fractures but did not present with RCTs. Results: Among the 11 collagens and 14 non-collagenous protein (NCP) genes examined in this study, COL3A1 and COL10A1 showed a significant increase, whereas COL4A1 and COL14A1 showed a tendency to decrease compared to those in the normal group. ACAN significantly increased by 8.92-fold (p < 0.001) compared to that in the normal group, whereas DCN and LUM showed a tendency to decrease. FN1 and TNC increased significantly by 3.47-fold (p = 0.003) and 5.38-fold (p = 0.005), respectively, and the genes ELN, LAMA2, and THBS1 were all significantly reduced compared to those in the normal group. In the NCPs, almost all the genes with increased expression levels had the highest level in small size RCTs, and gene expression decreased as the size increased. The 3 proteoglycans (ACAN, BGN, and FMOD) showed the highest levels of expression in small size RCTs compared to those in the normal group, and 5 glycoproteins (COMP, FBN1, FN1, HAPLN1, and TNC) also showed the highest expression in small size RCTs. Conclusions We confirmed that most of the detected extracellular matrix gene expression changes were related to the size of the full-thickness RCTs. In NCPs, gene expression was increased in small-size tears, and gene expression levels were significantly reduced when the size increased.

Background: To investigate the feasibility of the antegrade supraspinatus advancement (ASSA), which could be executed entirely arthroscopically without requiring a medial incision; to evaluate the impact of the ASSA on the lateral excursion of the torn end of the supraspinatus in retracted irreducible rotator cuff tears (RIRCTs); and to assess the safety and efficacy of arthroscopic rotator cuff repair with the ASSA. Methods: A total of 57 patients with RIRCTs who underwent the ASSA and were followed up for at least a year with magnetic resonance imaging (MRI) were included. The RIRCT was defined as the lateral excursion grade C (coverage less than the medial half of the greater tuberosity) or D (exposure of the glenohumeral joint). Clinical outcomes assessed nerve injury, pain, range of motion, strength, functional scores, and overall satisfaction and function. Structural outcomes evaluated the retear rate, fatty infiltration, and muscle atrophy of the rotator cuff muscles. The baseline for these structural measurements was time-zero MRIs. Results: The ASSA was feasibly performed all arthroscopically without a medial incision. There was no suprascapular nerve injury during the follow-up. The ASSA increased lateral excursion of the torn end in 86% of the patients from C or D to A or B. The ASSA significantly reduced pain and improved function of the shoulder at the final follow-up. All 11 patients who had had pseudoparalysis prior to repair regained the ability to raise their arm. The retear rate after the ASSA was 18.4%. Conclusions This study demonstrated that the ASSA can be safely and effectively performed all arthroscopically, significantly increasing the lateral excursion of the supraspinatus, thereby ensuring successful rotator cuff repair. This leads to a superior quality of repair, which consequently results in better clinical and structural outcomes, including the reversal of pseudoparalysis.

Background: This study aimed to investigate changes in gene expression related to matrix synthesis in individuals with fullthickness rotator cuff tears (RCTs) and normal tendon tissues. The study also aimed to examine the differences in gene expression according to 4 distinct tear sizes. Methods: A total of 12 patients with full-thickness RCTs were included in the study, all of whom underwent arthroscopic rotator cuff repair. The RCTs were stratified by size into small, medium, large, and massive. Tendon samples were harvested from the midpoint between the lateral end of the torn tendon and the musculotendinous junction. Subsequent analysis of the tissue samples revealed the mRNA expression levels of 11 collagen types, 6 proteoglycans, and 8 glycoproteins through real-time polymerase chain reaction techniques. For control purposes, supraspinatus tendon tissue was sourced from 3 patients who had proximal humerus fractures but did not present with RCTs. Results: Among the 11 collagens and 14 non-collagenous protein (NCP) genes examined in this study, COL3A1 and COL10A1 showed a significant increase, whereas COL4A1 and COL14A1 showed a tendency to decrease compared to those in the normal group. ACAN significantly increased by 8.92-fold (p < 0.001) compared to that in the normal group, whereas DCN and LUM showed a tendency to decrease. FN1 and TNC increased significantly by 3.47-fold (p = 0.003) and 5.38-fold (p = 0.005), respectively, and the genes ELN, LAMA2, and THBS1 were all significantly reduced compared to those in the normal group. In the NCPs, almost all the genes with increased expression levels had the highest level in small size RCTs, and gene expression decreased as the size increased. The 3 proteoglycans (ACAN, BGN, and FMOD) showed the highest levels of expression in small size RCTs compared to those in the normal group, and 5 glycoproteins (COMP, FBN1, FN1, HAPLN1, and TNC) also showed the highest expression in small size RCTs. Conclusions We confirmed that most of the detected extracellular matrix gene expression changes were related to the size of the full-thickness RCTs. In NCPs, gene expression was increased in small-size tears, and gene expression levels were significantly reduced when the size increased.

Background: To investigate the feasibility of the antegrade supraspinatus advancement (ASSA), which could be executed entirely arthroscopically without requiring a medial incision; to evaluate the impact of the ASSA on the lateral excursion of the torn end of the supraspinatus in retracted irreducible rotator cuff tears (RIRCTs); and to assess the safety and efficacy of arthroscopic rotator cuff repair with the ASSA. Methods: A total of 57 patients with RIRCTs who underwent the ASSA and were followed up for at least a year with magnetic resonance imaging (MRI) were included. The RIRCT was defined as the lateral excursion grade C (coverage less than the medial half of the greater tuberosity) or D (exposure of the glenohumeral joint). Clinical outcomes assessed nerve injury, pain, range of motion, strength, functional scores, and overall satisfaction and function. Structural outcomes evaluated the retear rate, fatty infiltration, and muscle atrophy of the rotator cuff muscles. The baseline for these structural measurements was time-zero MRIs. Results: The ASSA was feasibly performed all arthroscopically without a medial incision. There was no suprascapular nerve injury during the follow-up. The ASSA increased lateral excursion of the torn end in 86% of the patients from C or D to A or B. The ASSA significantly reduced pain and improved function of the shoulder at the final follow-up. All 11 patients who had had pseudoparalysis prior to repair regained the ability to raise their arm. The retear rate after the ASSA was 18.4%. Conclusions This study demonstrated that the ASSA can be safely and effectively performed all arthroscopically, significantly increasing the lateral excursion of the supraspinatus, thereby ensuring successful rotator cuff repair. This leads to a superior quality of repair, which consequently results in better clinical and structural outcomes, including the reversal of pseudoparalysis.

This study evaluates the biomechanical effects of acellular dermal matrix (ADM) patch augmentation in a rotator cuff repair model and determines the effect of medial knot tying on time-zero stability. Methods: A biomechanical study was conducted using a porcine flexor digitorum profundus tendon model. Eighteen specimens were assigned to three groups: non-patched repair with medial row knot tying (n=5), patch-augmented repair without medial row knot tying (n=4), and patch-augmented repair with medial row knot tying (n=4). All repairs were performed using a standardized double-row suture bridge technique. Biomechanical testing assessed elongation, strain, load to failure, and construct stiffness at time zero. Results: Patch augmentation without medial row knot tying resulted in significantly greater tendon elongation (12.9±6.5 mm) than nonpatched repairs (5.0±5.3 mm, P=0.016) and patch-augmented repairs with medial row knot tying (4.4±4.4 mm, P=0.027). Similarly, strain was significantly higher in the patch-augmented group without medial knot tying (75.8%±42.9%) than in the non-patched repair (35.2%±38.9%, P=0.028) and patch-augmented repair with medial knot tying groups (29.1%±28.9%, P=0.052). However, load to failure did not differ significantly among the groups (P>0.05). Conclusions: ADM patch augmentation did not enhance time-zero mechanical strength in the tested conditions, though biomechanical advantages might emerge after integration to the tendon. In addition, patch augmentation without medial row knot tying showed the highest elongation and strain among groups, potentially reducing the stability of the repair. Level of evidence: V, controlled laboratory study