Prostaglandin E2 (PGE2) Exerts Biphasic Effects on Human Tendon Stem Cells

Zhang, Jianying; Wang, James H.‐C.

doi:10.1371/journal.pone.0087706

Cited by 35 publications

(26 citation statements)

References 39 publications

(42 reference statements)

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“…Further, hTSCs exposed to high levels of PGE 2 also expressed high levels of non-tenocyte markers PPARγ, collagen II and osteocalcin, when implanted into rats [33] and lead to non-tendinous tissue formation. Taken together, these findings suggest that factors such as aging, excessive exercise and high PGE 2 levels can induce aberrant differentiation of TSCs in otherwise healthy tendons.…”

Section: Discussionmentioning

confidence: 99%

Moderate Exercise Mitigates the Detrimental Effects of Aging on Tendon Stem Cells

Zhang

Wang

2015

PLoS ONE

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Aging is known to cause tendon degeneration whereas moderate exercise imparts beneficial effects on tendons. Since stem cells play a vital role in maintaining tissue integrity, in this study we aimed to define the effects of aging and moderate exercise on tendon stem/progenitor cells (TSCs) using in vitro and in vivo models. TSCs derived from aging mice (9 and 24 months) proliferated significantly slower than TSCs obtained from young mice (2.5 and 5 months). In addition, expression of the stem cell markers Oct-4, nucleostemin (NS), Sca-1 and SSEA-1 in TSCs decreased in an age-dependent manner. Interestingly, moderate mechanical stretching (4%) of aging TSCs in vitro significantly increased the expression of the stem cell marker, NS, but 8% stretching decreased NS expression. Similarly, 4% mechanical stretching increased the expression of Nanog, another stem cell marker, and the tenocyte-related genes, collagen I and tenomodulin. However, 8% stretching increased expression of the non-tenocyte-related genes, LPL, Sox-9 and Runx-2, while 4% stretching had minimal effects on the expression of these genes. In the in vivo study, moderate treadmill running (MTR) of aging mice (9 months) resulted in the increased proliferation rate of aging TSCs in culture, decreased lipid deposition, proteoglycan accumulation and calcification, and increased the expression of NS in the patellar tendons. These findings indicate that while aging impairs the proliferative ability of TSCs and reduces their stemness, moderate exercise can mitigate the deleterious effects of aging on TSCs and therefore may be responsible for decreased aging-induced tendon degeneration.

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Section: Discussionmentioning

confidence: 99%

Moderate Exercise Mitigates the Detrimental Effects of Aging on Tendon Stem Cells

Zhang

Wang

2015

PLoS ONE

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“…A recent study reported that culturing TSCs along with insulin-like growth factor 1 (IGF-1) for 28 days retained multipotency in TSCs, and upregulated decorin and scleraxis expression (33). In addition, hypoxic culture conditions and low levels of PGE 2 could also enhance the stemness of TSCs in culture (34, 35). Second, the age of the donor might significantly affect the outcome of TSC treatments.…”

Section: Use Of Tscs To Treat Tendon Injuriesmentioning

confidence: 99%

Application of Tendon Stem/Progenitor Cells and Platelet-Rich Plasma to Treat Tendon Injuries

Wang

Nirmala

2016

Operative Techniques in Orthopaedics

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Tendon injuries like tendinopathy are a serious healthcare problem in the United States. However, current treatments for tendon injuries are largely palliative. Biologics treatments, including tendon stem/progenitor cells (TSCs) and platelet rich plasma (PRP) hold great potential to effectively treat tendon injuries. TSCs are tendon specific stem cells and have the ability to differentiate into tenocytes, the resident tendon cells responsible for tendon homeostasis and tendon repair in case of an injury. TSCs can also self-renew and thus can replenish the tendon with tendon cells (TSCs and tenocytes) to maintain a healthy tendon. The action of PRP can be complementary; PRP can augment and accelerate tendon healing by supplying abundant growth factors contained in platelets, and fibrin matrix, which functions as a natural conducive scaffold to facilitate tissue healing. This article provides a summary of the findings in recent basic and clinical studies on the applications of TSCs and PRP to the treatment of tendon injuries. It also outlines the challenges facing their applications in clinical settings. In particular, the controversy surrounding the efficacy of PRP treatment for tendon injuries are analyzed and solutions are suggested.

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“…After washing the hydrogels three times with PBS, fluorescence microscopy was performed using an Olympus IX83 microscope with a spinning disc confocal attachment. Brightfield and fluorescent‐channel images of spheres were analyzed using the ImageJ software (NIH) for the semiquantification of EdU‐positivity as described previously (Gansau & Buckley, ; Kilani et al, ; Zhang & Wang, ; Zhang, Pan, Im, Fu, & Wang, ). The fraction of EdU‐positivity was calculated as the area of the positively‐stained cells divided by the total area of the spheroid.…”

Section: Methodsmentioning

confidence: 99%

“…Brightfield and fluorescent-channel images of spheres were analyzed using the ImageJ software (NIH) for the semiquantification of EdUpositivity as described previously (Gansau & Buckley, 2018;Kilani et al, 2003;Zhang & Wang, 2014;Zhang, Pan, Im, Fu, & Wang, 2011).…”

Section: -Ethynyl-2′-deoxyuridine Assaymentioning

confidence: 99%

Three‐dimensional biomimetic hyaluronic acid hydrogels to investigate glioblastoma stem cell behaviors

Nakod

Kim

Rao

2019

Biotech & Bioengineering

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Glioblastoma multiforme (GBM) is the deadliest form of primary brain tumor. GBM tumors are highly heterogeneous, being composed of tumor cells as well as glioblastoma stem cells (GSCs) that contribute to drug resistance and tumor recurrence following treatment. To develop therapeutic strategies, an improved understanding of GSC behavior in their microenvironment is critical. Herein, we have employed three‐dimensional (3D) hyaluronic acid (HA) hydrogels that allow the incorporation of brain microenvironmental cues to investigate GSC behavior. U87 cell line and patient‐derived D456 cells were cultured as suspension cultures (serum‐free) and adherently (in the presence of serum) and were then encapsulated in HA hydrogels. We observed that all the seeded single cells expanded and formed spheres, and the size of the spheres increased with time. Increasing the initial cell seeding density of cells influenced the sphere size distribution. Interestingly, clonal expansion of serum‐free grown tumor cells in HA hydrogels was observed. Also, stemness marker expression of serum and/or serum‐free grown cells was altered when cultured in HA hydrogels. Finally, we demonstrated that HA hydrogels can support long‐term GSC culture (up to 60 days) with retention of stemness markers. Overall, such biomimetic culture systems could further our understanding of the microenvironmental regulation of GSC phenotypes.

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Prostaglandin E2 (PGE2) Exerts Biphasic Effects on Human Tendon Stem Cells

Cited by 35 publications

References 39 publications

Moderate Exercise Mitigates the Detrimental Effects of Aging on Tendon Stem Cells

Moderate Exercise Mitigates the Detrimental Effects of Aging on Tendon Stem Cells

Application of Tendon Stem/Progenitor Cells and Platelet-Rich Plasma to Treat Tendon Injuries

Three‐dimensional biomimetic hyaluronic acid hydrogels to investigate glioblastoma stem cell behaviors

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