A Cd9+Cd271+ stem/progenitor population and the SHP2 pathway contribute to neonatal-to-adult switching that regulates tendon maturation

Fan, Chunmei; Zhao, Yanyan; Chen, Yangwu; Qin, Tian; Lin, Junxin; Han, Shan; Yan, Ruojin; Lei, Tingyun; Xie, Yuanhao; Wang, Tingzhang; Gu, Shen; Ouyang, Hongwei; Shen, Wei; Yin, Zi; Chen, Xiao

doi:10.1016/j.celrep.2022.110762

Cited by 7 publications

(8 citation statements)

References 62 publications

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“…In this regard a recent study on the development of mouse tendon tissue indicated that the time interval between postnatal day 4 (P4) and P12 is the critical stage for postnatal tendon maturation [46]. Specifically, this study demonstrated that the gene expression of scleraxis, mohawk, type IA1 collagen and tenomodulin peaked at P4, followed by a substantial reduction in the relative amount of cells in the tendon tissue between P14 and P28 [46]. In a study on human fetal posterior tibial tendons samples obtained from 22-28 week old fetuses showed a higher relative amount of cells in the tendon tissue than samples obtained from 32-38 week old fetuses [28].…”

Section: Discussionmentioning

confidence: 99%

“…A clinical study found no improvement of anterior cruciate ligament reconstruction by injection of UA-ADRCs into a bone-tendon-bone (BTB) graft derived from the patella and related tendons compared without injection of UA-ADRCs [46]. However, the description of the infiltration procedure of the BTB graft with UA-ADRCs in that study [52] does not exclude the cells were injected mostly into the tendon part of the BTB graft, which may have limited the success of their approach.…”

Section: Discussionmentioning

confidence: 99%

“…21a). In this regard a recent study on the development of mouse tendon tissue indicated that the time interval between postnatal day 4 (P4) and P12 is the critical stage for postnatal tendon maturation [46]. Specifically, this study demonstrated that the gene expression of scleraxis, mohawk, type IA1 collagen and tenomodulin peaked at P4, followed by a substantial reduction in the relative amount of cells in the tendon tissue between P14 and P28 [46].…”

Section: Discussionmentioning

confidence: 99%

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New, biomechanically sound tendon tissue after injection of uncultured, autologous, adipose derived regenerative cells in partial Achilles tendon defects in rabbits

Schmitz,

Alt,

Würfel

et al. 2024

Preprint

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BackgroundCurrent management options for partial tendon tears may not offer future potential to heal tissue and improve clinical results. This study tested the hypothesis that treatment of a partial rabbit common calcaneus tendon (CCT) defect with uncultured, autologous, adipose derived regenerative cells (UA-ADRCs) enables regenerative healing without scar formation, as recently observed in a biopsy of a human supraspinatus tendon.MethodsA full-thickness hole (diameter, 3 mm) was punched into the midsubstance of the right gastrocnemius tendon (GT; which is a part of the CCT) of adult, female New Zealand white rabbits. Immediately thereafter the rabbits were treated by application of an averaged 28.3×106UA-ADRCs in 0.5 ml lactated Ringer’s solution (RLS) into the GT defect and surrounding tendon tissue, or underwent sham treatment. Rabbits were sacrificed either four weeks (W4) or twelve weeks (W12) post-treatment, and the CCTs were investigated using histology, immunohistochemistry and non-destructive biomechanical testing.ResultsNewly formed connective tissue was consistent with the formation of new tendon tissue after treatment with UA-ADRCs, and with the formation of scar tissue after sham treatment, at both W4 and W12 post-treatment. Biomechanical testing demonstrated a significantly higher mean percent relaxation after treatment with UA-ADRCs than after sham treatment (p < 0.05), and significant, negative correlations between the peak stress as well as the equilibrium stress and the cross-sectional area of the CCT (p < 0.05) after treatment with UA-ADRCs but not after sham treatment.ConclusionsManagement of partial tendon tears with UA-ADRCs has the potential to be truly “structure-modifying”.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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New, biomechanically sound tendon tissue after injection of uncultured, autologous, adipose derived regenerative cells in partial Achilles tendon defects in rabbits

Schmitz,

Alt,

Würfel

et al. 2024

Preprint

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show abstract

“…Recent studies appear to confirm a key role for neurotropic axis molecules, such as NGF and its downstream cognates EGR1 and EGR2, in managing the transition from immature tendon cells to tenocytes ( 41 ), thus accompanying the structural evolution from neonate to early post-natal tendons ( 42 ), which recognize an increased level of complexity.…”

Section: Discussionmentioning

confidence: 99%

Mammal comparative tendon biology: advances in regulatory mechanisms through a computational modeling

Peserico¹,

Barboni²,

Russo³

et al. 2023

Front. Vet. Sci.

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There is high clinical demand for the resolution of tendinopathies, which affect mainly adult individuals and animals. Tendon damage resolution during the adult lifetime is not as effective as in earlier stages where complete restoration of tendon structure and property occurs. However, the molecular mechanisms underlying tendon regeneration remain unknown, limiting the development of targeted therapies. The research aim was to draw a comparative map of molecules that control tenogenesis and to exploit systems biology to model their signaling cascades and physiological paths. Using current literature data on molecular interactions in early tendon development, species-specific data collections were created. Then, computational analysis was used to construct Tendon NETworks in which information flow and molecular links were traced, prioritized, and enriched. Species-specific Tendon NETworks generated a data-driven computational framework based on three operative levels and a stage-dependent set of molecules and interactions (embryo–fetal or prepubertal) responsible, respectively, for signaling differentiation and morphogenesis, shaping tendon transcriptional program and downstream modeling of its fibrillogenesis toward a mature tissue. The computational network enrichment unveiled a more complex hierarchical organization of molecule interactions assigning a central role to neuro and endocrine axes which are novel and only partially explored systems for tenogenesis. Overall, this study emphasizes the value of system biology in linking the currently available disjointed molecular data, by establishing the direction and priority of signaling flows. Simultaneously, computational enrichment was critical in revealing new nodes and pathways to watch out for in promoting biomedical advances in tendon healing and developing targeted therapeutic strategies to improve current clinical interventions.

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“…Hence, an overall understanding of tendon differentiation and molecular pathways is needed to develop strategies for restoring tendon function. Fan et al 119 identified the regulatory role of a nerve growth factor-secreting Cd9 + Cd271 + tendon stem/progenitor cluster in tendon maturation and the NGF/SHP2 pathway. Nakajima T et al 120 used scRNA-seq to analyze the developmental trajectory of induced pluripotent stem cell-derived tenocytes and found that cell grafting contributed to efficient motor function recovery after Achilles tendon damage in rats, implying that human pluripotent stem cell-derived tenocytes had therapeutic potential in the context of tendon injury.…”

Section: Introductionmentioning

confidence: 99%

Single-cell RNA sequencing in orthopedic research

et al. 2023

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Although previous RNA sequencing methods have been widely used in orthopedic research and have provided ideas for therapeutic strategies, the specific mechanisms of some orthopedic disorders, including osteoarthritis, lumbar disc herniation, rheumatoid arthritis, fractures, tendon injuries, spinal cord injury, heterotopic ossification, and osteosarcoma, require further elucidation. The emergence of the single-cell RNA sequencing (scRNA-seq) technique has introduced a new era of research on these topics, as this method provides information regarding cellular heterogeneity, new cell subtypes, functions of novel subclusters, potential molecular mechanisms, cell-fate transitions, and cell‒cell interactions that are involved in the development of orthopedic diseases. Here, we summarize the cell subpopulations, genes, and underlying mechanisms involved in the development of orthopedic diseases identified by scRNA-seq, improving our understanding of the pathology of these diseases and providing new insights into therapeutic approaches.

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A Cd9+Cd271+ stem/progenitor population and the SHP2 pathway contribute to neonatal-to-adult switching that regulates tendon maturation

Cited by 7 publications

References 62 publications

New, biomechanically sound tendon tissue after injection of uncultured, autologous, adipose derived regenerative cells in partial Achilles tendon defects in rabbits

New, biomechanically sound tendon tissue after injection of uncultured, autologous, adipose derived regenerative cells in partial Achilles tendon defects in rabbits

Mammal comparative tendon biology: advances in regulatory mechanisms through a computational modeling

Single-cell RNA sequencing in orthopedic research

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