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Article ; Online: Cell migration: implications for repair and regeneration in joint disease.

Qu, Feini / Guilak, Farshid / Mauck, Robert L

2019 Volume 15, Issue 3, Page(s) 167–179

Abstract: Connective tissues within the synovial joints are characterized by their dense extracellular matrix and sparse cellularity. With injury or disease, however, tissues commonly experience an influx of cells owing to proliferation and migration of endogenous ...

Abstract	Connective tissues within the synovial joints are characterized by their dense extracellular matrix and sparse cellularity. With injury or disease, however, tissues commonly experience an influx of cells owing to proliferation and migration of endogenous mesenchymal cell populations, as well as invasion of the tissue by other cell types, including immune cells. Although this process is critical for successful wound healing, aberrant immune-mediated cell infiltration can lead to pathological inflammation of the joint. Importantly, cells of mesenchymal or haematopoietic origin use distinct modes of migration and thus might respond differently to similar biological cues and microenvironments. Furthermore, cell migration in the physiological microenvironment of musculoskeletal tissues differs considerably from migration in vitro. This Review addresses the complexities of cell migration in fibrous connective tissues from three separate but interdependent perspectives: physiology (including the cellular and extracellular factors affecting 3D cell migration), pathophysiology (cell migration in the context of synovial joint autoimmune disease and injury) and tissue engineering (cell migration in engineered biomaterials). Improved understanding of the fundamental mechanisms governing interstitial cell migration might lead to interventions that stop invasion processes that culminate in deleterious outcomes and/or that expedite migration to direct endogenous cell-mediated repair and regeneration of joint tissues.
MeSH term(s)	Animals ; Cell Movement/physiology ; Humans ; Joint Diseases/pathology ; Joint Diseases/physiopathology ; Regeneration/physiology
Language	English
Publishing date	2019-01-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2491532-4
ISSN	1759-4804 ; 1759-4790
ISSN (online)	1759-4804
ISSN	1759-4790
DOI	10.1038/s41584-018-0151-0
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Article ; Online: The role of PIEZO ion channels in the musculoskeletal system.

Savadipour, Alireza / Palmer, Daniel / Ely, Erica V / Collins, Kelsey H / Garcia-Castorena, Jaquelin M / Harissa, Zainab / Kim, Yu Seon / Oestrich, Arin / Qu, Feini / Rashidi, Neda / Guilak, Farshid

American journal of physiology. Cell physiology

2023 Volume 324, Issue 3, Page(s) C728–C740

Abstract: PIEZO1 and PIEZO2 are mechanosensitive cation channels that are highly expressed in numerous tissues throughout the body and exhibit diverse, cell-specific functions in multiple organ systems. Within the musculoskeletal system, PIEZO1 functions to ... ...

Abstract	PIEZO1 and PIEZO2 are mechanosensitive cation channels that are highly expressed in numerous tissues throughout the body and exhibit diverse, cell-specific functions in multiple organ systems. Within the musculoskeletal system, PIEZO1 functions to maintain muscle and bone mass, sense tendon stretch, and regulate senescence and apoptosis in response to mechanical stimuli within cartilage and the intervertebral disc. PIEZO2 is essential for transducing pain and touch sensations as well as proprioception in the nervous system, which can affect musculoskeletal health. PIEZO1 and PIEZO2 have been shown to act both independently as well as synergistically in different cell types. Conditions that alter PIEZO channel mechanosensitivity, such as inflammation or genetic mutations, can have drastic effects on these functions. For this reason, therapeutic approaches for PIEZO-related disease focus on altering PIEZO1 and/or PIEZO2 activity in a controlled manner, either through inhibition with small molecules, or through dietary control and supplementation to maintain a healthy cell membrane composition. Although many opportunities to better understand PIEZO1 and PIEZO2 remain, the studies summarized in this review highlight how crucial PIEZO channels are to musculoskeletal health and point to promising possible avenues for their modulation as a therapeutic target.
MeSH term(s)	Cell Membrane/metabolism ; Ion Channels/genetics ; Ion Channels/metabolism ; Mechanotransduction, Cellular ; Muscles ; Musculoskeletal System/metabolism ; Humans
Chemical Substances	Ion Channels ; PIEZO1 protein, human ; PIEZO2 protein, human
Language	English
Publishing date	2023-01-30
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00544.2022
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Article ; Online: Transcriptomic analysis of bone and fibrous tissue morphogenesis during digit tip regeneration in the adult mouse.

Qu, Feini / Palte, Ilan C / Gontarz, Paul M / Zhang, Bo / Guilak, Farshid

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2020 Volume 34, Issue 7, Page(s) 9740–9754

Abstract: Humans have limited regenerative potential of musculoskeletal tissues following limb or digit loss. The murine digit has been used to study mammalian regeneration, where stem/progenitor cells (the "blastema") completely regenerate the digit tip after ... ...

Abstract	Humans have limited regenerative potential of musculoskeletal tissues following limb or digit loss. The murine digit has been used to study mammalian regeneration, where stem/progenitor cells (the "blastema") completely regenerate the digit tip after distal, but not proximal, amputation. However, the molecular mechanisms responsible for this response remain to be determined. Here, we evaluated the spatiotemporal formation of bone and fibrous tissues after level-dependent amputation of the murine terminal phalanx and quantified the transcriptome of the repair tissue. Distal (regenerative) and proximal (non-regenerative) amputations showed significant differences in temporal gene expression and tissue regrowth over time. Genes that direct skeletal system development and limb morphogenesis are transiently upregulated during blastema formation and differentiation, including distal Hox genes. Overall, our results suggest that digit tip regeneration is controlled by a gene regulatory network that recapitulates aspects of limb development, and that failure to activate this developmental program results in fibrotic wound healing.
MeSH term(s)	Animals ; Bone and Bones/cytology ; Bone and Bones/metabolism ; Cell Differentiation ; Extremities/physiology ; Female ; Mice ; Mice, Inbred C57BL ; Morphogenesis ; Osteogenesis ; Regeneration ; Transcriptome ; Wound Healing
Language	English
Publishing date	2020-06-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202000330R
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Zs.A 2266: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 296: Show issues

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Article ; Online: Programmed biomolecule delivery to enable and direct cell migration for connective tissue repair

Feini Qu / Julianne L. Holloway / John L. Esterhai / Jason A. Burdick / Robert L. Mauck

Nature Communications, Vol 8, Iss 1, Pp 1-

2017 Volume 11

Abstract: Dense connective tissues do not easily heal, in part due to a low supply of reparative cells. Here, the authors develop a fibrous scaffold for meniscal repair that sequentially releases collagenase and a growth factor at the injury site, breaking down ... ...

Abstract	Dense connective tissues do not easily heal, in part due to a low supply of reparative cells. Here, the authors develop a fibrous scaffold for meniscal repair that sequentially releases collagenase and a growth factor at the injury site, breaking down the extracellular matrix and recruiting endogenous cells.
Keywords	Science ; Q
Language	English
Publishing date	2017-11-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Programmed biomolecule delivery to enable and direct cell migration for connective tissue repair

Feini Qu / Julianne L. Holloway / John L. Esterhai / Jason A. Burdick / Robert L. Mauck

Nature Communications, Vol 8, Iss 1, Pp 1-

2017 Volume 11

Abstract	Dense connective tissues do not easily heal, in part due to a low supply of reparative cells. Here, the authors develop a fibrous scaffold for meniscal repair that sequentially releases collagenase and a growth factor at the injury site, breaking down the extracellular matrix and recruiting endogenous cells.
Keywords	Science ; Q
Language	English
Publishing date	2017-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Impacts of maturation on the micromechanics of the meniscus extracellular matrix.

Li, Qing / Wang, Chao / Han, Biao / Qu, Feini / Qi, Hao / Li, Christopher Y / Mauck, Robert L / Han, Lin

Journal of biomechanics

2018 Volume 72, Page(s) 252–257

Abstract: To elucidate how maturation impacts the structure and mechanics of meniscus extracellular matrix (ECM) at the length scale of collagen fibrils and fibers, we tested the micromechanical properties of fetal and adult bovine menisci via atomic force ... ...

Abstract	To elucidate how maturation impacts the structure and mechanics of meniscus extracellular matrix (ECM) at the length scale of collagen fibrils and fibers, we tested the micromechanical properties of fetal and adult bovine menisci via atomic force microscopy (AFM)-nanoindentation. For circumferential fibers, we detected significant increase in the effective indentation modulus, E
MeSH term(s)	Animals ; Cattle ; Extracellular Matrix/physiology ; Female ; Fetus ; Fibrillar Collagens/physiology ; Meniscus/physiology ; Microscopy, Atomic Force
Chemical Substances	Fibrillar Collagens
Language	English
Publishing date	2018-03-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	218076-5
ISSN	1873-2380 ; 0021-9290
ISSN (online)	1873-2380
ISSN	0021-9290
DOI	10.1016/j.jbiomech.2018.02.037
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Zs.A 700: Show issues

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Article ; Online: Measuring clinically relevant knee motion with a self-calibrated wearable sensor.

Hullfish, Todd J / Qu, Feini / Stoeckl, Brendan D / Gebhard, Peter M / Mauck, Robert L / Baxter, Josh R

Journal of biomechanics

2019 Volume 89, Page(s) 105–109

Abstract: Low-cost sensors provide a unique opportunity to continuously monitor patient progress during rehabilitation; however, these sensors have yet to demonstrate the fidelity and lack the calibration paradigms necessary to be viable tools for clinical ... ...

Abstract	Low-cost sensors provide a unique opportunity to continuously monitor patient progress during rehabilitation; however, these sensors have yet to demonstrate the fidelity and lack the calibration paradigms necessary to be viable tools for clinical research. The purpose of this study was to validate a low-cost wearable sensor that accurately measured peak knee extension during clinical exercises and needed no additional equipment for calibration. Sagittal plane knee motion was quantified using a 9-axis motion sensor and directly compared to motion capture data. The motion sensor measured the field strength of a strong earth magnet secured to the distal femur, which was correlated with knee angle during a simple calibration process. Peak knee motions and kinematic patterns were compared with motion capture data using paired t-tests and cross correlation, respectively. Peak extension values during seated knee extensions were accurate within 5 degrees across all subjects (root mean square error: 2.6 degrees, P = 0.29). Knee flexion during gait strongly correlated (0.84 ≤ r
MeSH term(s)	Adult ; Biomechanical Phenomena ; Calibration ; Femur/physiology ; Gait ; Humans ; Knee/physiology ; Male ; Monitoring, Physiologic/instrumentation ; Movement ; Wearable Electronic Devices
Language	English
Publishing date	2019-04-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	218076-5
ISSN	1873-2380 ; 0021-9290
ISSN (online)	1873-2380
ISSN	0021-9290
DOI	10.1016/j.jbiomech.2019.04.003
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Article ; Online: Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues.

Heo, Su-Jin / Song, Kwang Hoon / Thakur, Shreyasi / Miller, Liane M / Cao, Xuan / Peredo, Ana P / Seiber, Breanna N / Qu, Feini / Driscoll, Tristan P / Shenoy, Vivek B / Lakadamyali, Melike / Burdick, Jason A / Mauck, Robert L

Science advances

2020 Volume 6, Issue 25, Page(s) eaax5083

Abstract: Dense matrices impede interstitial cell migration and subsequent repair. We hypothesized that nuclear stiffness is a limiting factor in migration and posited that repair could be expedited by transiently decreasing nuclear stiffness. To test this, we ... ...

Abstract	Dense matrices impede interstitial cell migration and subsequent repair. We hypothesized that nuclear stiffness is a limiting factor in migration and posited that repair could be expedited by transiently decreasing nuclear stiffness. To test this, we interrogated the interstitial migratory capacity of adult meniscal cells through dense fibrous networks and adult tissue before and after nuclear softening via the application of a histone deacetylase inhibitor, Trichostatin A (TSA) or knockdown of the filamentous nuclear protein Lamin A/C. Our results show that transient softening of the nucleus improves migration through microporous membranes, electrospun fibrous matrices, and tissue sections and that nuclear properties and cell function recover after treatment. We also showed that biomaterial delivery of TSA promoted in vivo cellularization of scaffolds by endogenous cells. By addressing the inherent limitations to repair imposed by nuclear stiffness, this work defines a new strategy to promote the repair of damaged dense connective tissues.
Keywords	covid19
Language	English
Publishing date	2020-06-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.aax5083
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Article ; Online: Programmed biomolecule delivery to enable and direct cell migration for connective tissue repair.

Qu, Feini / Holloway, Julianne L / Esterhai, John L / Burdick, Jason A / Mauck, Robert L

Nature communications

2017 Volume 8, Issue 1, Page(s) 1780

Abstract: Dense connective tissue injuries have limited repair, due to the paucity of cells at the wound site. We hypothesize that decreasing the density of the local extracellular matrix (ECM) in conjunction with releasing chemoattractive signals increases ... ...

Abstract	Dense connective tissue injuries have limited repair, due to the paucity of cells at the wound site. We hypothesize that decreasing the density of the local extracellular matrix (ECM) in conjunction with releasing chemoattractive signals increases cellularity and tissue formation after injury. Using the knee meniscus as a model system, we query interstitial cell migration in the context of migratory barriers using a novel tissue Boyden chamber and show that a gradient of platelet-derived growth factor-AB (PDGF-AB) expedites migration through native tissue. To implement these signals in situ, we develop nanofibrous scaffolds with distinct fiber fractions that sequentially release active collagenase (to increase ECM porosity) and PDGF-AB (to attract endogenous cells) in a localized and coordinated manner. We show that, when placed into a meniscal defect, the controlled release of collagenase and PDGF-AB increases cellularity at the interface and within the scaffold, as well as integration with the surrounding tissue.
MeSH term(s)	Animals ; Cattle ; Cell Movement ; Cells, Cultured ; Collagenases/metabolism ; Connective Tissue Cells/cytology ; Connective Tissue Cells/metabolism ; Extracellular Matrix/chemistry ; Extracellular Matrix/metabolism ; Male ; Meniscus/injuries ; Meniscus/metabolism ; Meniscus/physiopathology ; Platelet-Derived Growth Factor/metabolism ; Rats ; Regeneration ; Tissue Engineering ; Tissue Scaffolds/chemistry
Chemical Substances	Platelet-Derived Growth Factor ; platelet-derived growth factor AB ; Collagenases (EC 3.4.24.-)
Language	English
Publishing date	2017-11-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2041-1723
ISSN (online)	2041-1723
DOI	10.1038/s41467-017-01955-w
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Article ; Online: Maturation State and Matrix Microstructure Regulate Interstitial Cell Migration in Dense Connective Tissues.

Qu, Feini / Li, Qing / Wang, Xiao / Cao, Xuan / Zgonis, Miltiadis H / Esterhai, John L / Shenoy, Vivek B / Han, Lin / Mauck, Robert L

Scientific reports

2018 Volume 8, Issue 1, Page(s) 3295

Abstract: Few regenerative approaches exist for the treatment of injuries to adult dense connective tissues. Compared to fetal tissues, adult connective tissues are hypocellular and show limited healing after injury. We hypothesized that robust repair can occur in ...

Abstract	Few regenerative approaches exist for the treatment of injuries to adult dense connective tissues. Compared to fetal tissues, adult connective tissues are hypocellular and show limited healing after injury. We hypothesized that robust repair can occur in fetal tissues with an immature extracellular matrix (ECM) that is conducive to cell migration, and that this process fails in adults due to the biophysical barriers imposed by the mature ECM. Using the knee meniscus as a platform, we evaluated the evolving micromechanics and microstructure of fetal and adult tissues, and interrogated the interstitial migratory capacity of adult meniscal cells through fetal and adult tissue microenvironments with or without partial enzymatic digestion. To integrate our findings, a computational model was implemented to determine how changing biophysical parameters impact cell migration through these dense networks. Our results show that the micromechanics and microstructure of the adult meniscus ECM sterically hinder cell mobility, and that modulation of these ECM attributes via an exogenous matrix-degrading enzyme permits migration through this otherwise impenetrable network. By addressing the inherent limitations to repair imposed by the mature ECM, these studies may define new clinical strategies to promote repair of damaged dense connective tissues in adults.
MeSH term(s)	Adult ; Cell Movement/genetics ; Connective Tissue/growth & development ; Connective Tissue/injuries ; Extracellular Matrix/genetics ; Humans ; Leydig Cells/metabolism ; Male ; Meniscus/growth & development ; Meniscus/injuries ; Regenerative Medicine ; Tissue Scaffolds/chemistry
Language	English
Publishing date	2018-02-19
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-21212-4
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