Effects of cyclic stretching on anterior cruciate ligament-constructs fabricated from human MSCs and collagen type I gels

After an anterior cruciate ligament (ACL) injury, surgical reconstructions are necessary in most cases, either with autografts, allografts, or artificial ligaments. Potential tissue-engineered ligaments would circumvent the disadvantages apparent in these methods. While seeding of mesenchymal stem cells (MSCs) and fascia wrap could potentially improve tissue regeneration and mechanical properties, their exact roles were evaluated in the current study. Knitted biodegradable scaffolds of poly-L-lactic acid (PLLA) and poly-glycolic-lactic acid (PGLA) yarns were used to reconstruct ACL in 48 rabbits. These were divided into four equal groups: only knitted scaffolds were used in group I; knitted scaffolds and mesenchymal stem cells were used in group II; knitted scaffolds, MSCs, and fascia lata were used in group III; knitted scaffolds and fascia lata were used in group IV. Carboxyfluorescein diacetate (CFDA)-labeled MSCs were used to trace the fate of seeded cells in groups II and III. Histology, Western blot analysis, and mechanical properties of reconstructed ACL were analyzed after 20 weeks. Fibroblast ingrowths were seen in all four groups while CFDA-labeled MSCs could be found after 8 weeks of implantation in groups II and III. Both the amount of collagen type I and collagen type III in groups III and IV were significantly higher than in group II, which was much higher than in group I. Both maximal tensile loads and stiffness of the reconstructed ACLs in groups I, II, III, and IV were significantly lower than normal controls after 20 weeks of implantation. It is concluded that MSCs could promote synthesis of collagen type I and collagen type III in tissue-engineered ligaments, while fascia wraps have stronger effects. Both MSC seeding and fascia wrap could not enhance ultimate tensile load and stiffness.

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Mesenchymal stem cells from adipose tissue which have been differentiated into chondrocytes in three-dimensional culture express lubricin

Experimental Biology and Medicine ◽

10.1258/ebm.2011.011183 ◽

2011 ◽

Vol 236 (11) ◽

pp. 1333-1341 ◽

Cited By ~ 48

Author(s):

Giuseppe Musumeci ◽

Debora Lo Furno ◽

Carla Loreto ◽

Rosario Giuffrida ◽

Silvia Caggia ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Collagen Type ◽

Three Dimensional ◽

3D Culture ◽

Collagen Type I ◽

Type I ◽

Human Mscs ◽

Alternative Source

The present study focused on the isolation, cultivation and characterization of human mesenchymal stem cells (MSCs) from adipose tissue and on their differentiation into chondrocytes through the NH ChondroDiff medium. The main aim was to investigate some markers of biomechanical quality of cartilage, such as lubricin, and collagen type I and II. Little is known, in fact, about the ability of chondrocytes from human MSCs of adipose tissue to generate lubricin in three-dimensional (3D) culture. Lubricin, a 227.5-kDa mucinous glycoprotein, is known to play an important role in articular joint physiology, and the loss of accumulation of lubricin is thought to play a role in the pathology of osteoarthritis. Adipose tissue is an alternative source for the isolation of multipotent MSCs, which allows them to be obtained by a less invasive method and in larger quantities than from other sources. These cells can be isolated from cosmetic liposuctions in large numbers and easily grown under standard tissue culture conditions. 3D chondrocytes were assessed by histology (hematoxylin and eosin) and histochemistry (Alcian blue and Safranin-O/fast green staining). Collagen type I, II and lubricin expression was determined through immunohistochemistry and Western blot. The results showed that, compared with control cartilage and monolayer chondrocytes showing just collagen type I, chondrocytes from MSCs (CD44-, CD90- and CD105- positive; CD45-, CD14- and CD34-negative) of adipose tissue grown in nodules were able to express lubricin, and collagen type I and II, indicative of hyaline cartilage formation. Based on the function of lubricin in the joint cavity and disease and as a potential therapeutic agent, our results suggest that MSCs from adipose tissue are a promising cell source for tissue engineering of cartilage. Our results suggest that chondrocyte nodules producing lubricin could be a novel biotherapeutic approach for the treatment of cartilage abnormalities.

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Mechanical stretch in anterior cruciate ligament derived cells regulates type I collagen and decorin expression through extracellular signal-regulated kinase 1/2 pathway

Materials Science and Engineering C ◽

10.1016/s0928-4931(01)00314-9 ◽

2001 ◽

Vol 17 (1-2) ◽

pp. 91-94 ◽

Cited By ~ 7

Author(s):

Shigeru Miyaki ◽

Takashi Ushida ◽

Ken Nemoto ◽

Hitoshi Shimojo ◽

Akira Itabashi ◽

...

Keyword(s):

Anterior Cruciate Ligament ◽

Type I Collagen ◽

Cruciate Ligament ◽

Mechanical Stretch ◽

Type I ◽

Extracellular Signal Regulated Kinase ◽

Extracellular Signal ◽

Anterior Cruciate

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Gene Expression of Type I and Type III Collagen by Mechanical Stretch in Anterior Cruciate Ligament Cells

Cell Structure and Function ◽

10.1247/csf.27.139 ◽

2002 ◽

Vol 27 (3) ◽

pp. 139-144 ◽

Cited By ~ 114

Author(s):

Sung-Gon Kim ◽

Toshihiro Akaike ◽

Tadashi Sasagawa ◽

Yoriko Atomi ◽

Hisashi Kurosawa

Keyword(s):

Gene Expression ◽

Anterior Cruciate Ligament ◽

Cruciate Ligament ◽

Mechanical Stretch ◽

Type Iii Collagen ◽

Type I ◽

Type Iii ◽

Anterior Cruciate

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The Effect of Oral Contraceptive Hormones on Anterior Cruciate Ligament Strength

The American Journal of Sports Medicine ◽

10.1177/0363546519887167 ◽

2019 ◽

Vol 48 (1) ◽

pp. 85-92 ◽

Cited By ~ 2

Author(s):

Jaclyn A. Konopka ◽

Lauren Hsue ◽

Wenteh Chang ◽

Timothy Thio ◽

Jason L. Dragoo

Keyword(s):

Anterior Cruciate Ligament ◽

Matrix Metalloproteinase ◽

Female Athletes ◽

Cruciate Ligament ◽

Acl Injury ◽

Maximum Load ◽

Female Rats ◽

Type I ◽

Matrix Metalloproteinase 1 ◽

Anterior Cruciate

Background: Women are 2 to 9 times more likely to experience an anterior cruciate ligament (ACL) injury than men. Various hormones including relaxin, progesterone, and estrogen influence ACL strength. Oral contraceptives (OCs) alter these hormone levels; however, studies have yet to comprehensively compare different OCs’ effects on the ACL. Hypothesis: OCs with increased progestin-to-estrogen ratios will (1) increase ACL collagen expression, (2) decrease ACL matrix metalloproteinase expression, and (3) increase ACL strength. Study Design: Controlled laboratory study. Methods: Untreated female rats were compared with rats treated with 1 of 5 clinically used OCs: norethindrone (NE) only, NE plus ethinylestradiol (EE), etynodiol diacetate (ED) plus EE, norgestimate (NG) plus EE, and drospirenone (DS) plus EE. Doses were scaled from human doses to account for differences in bioavailability and body weight, and OCs were administered daily via oral gavage for 4 rat estrous cycles (20 days). A total of 36 rats were then sacrificed (6 rats/group). ACLs underwent biomechanical testing to assess ACL strength, stiffness, and maximum load before failure. ACL specimens were also isolated for quantitative real-time polymerase chain reaction analysis to assess collagen, matrix metalloproteinase, and relaxin receptor–1 expression. Results: While the primary structural property of interest (ACL maximum load before failure) was not significantly improved by OC treatment, the main material property of interest (ACL strength) in rats treated with NE only, DS + EE, ED + EE, and NE + EE was significantly increased compared with untreated controls ( P = .001, P = .004, P = .004, and P = .04, respectively). The order from strongest to weakest ACLs, which was also the same order as the highest to lowest progestin-to-estrogen ratios, was groups treated with NE only, DS + EE, ED + EE, NE + EE, and lastly NG + EE. Higher ratio formulations also increased the expression of type I collagen ( P = .02) and decreased the expression of matrix metalloproteinase–1 ( P = .04). Conclusion: OC formulations with higher progestin-to-estrogen ratios may be more protective for the ACL than formulations with lower ratios. Clinical Relevance: OC formulations with high progestin-to-estrogen ratios may benefit female athletes by reducing their ACL injury risk by decreasing the effects of relaxin on the ACL.

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