Human umbilical cord-derived mesenchymal stem cells and their chondroprogenitor derivatives reduced pain and inflammation signaling and promote regeneration in a rat intervertebral disc degeneration model

Ekram, Sobia; Khalid, Shumaila; Bashir, Imtiaz; Salim, Asmat; Khan, Irfan

doi:10.1007/s11010-021-04155-9

Cited by 29 publications

(35 citation statements)

References 53 publications

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“…Tissue processing for histological analysis was performed as previously described [ 32 , 33 ]. Briefly, native and DUC tissue were fixed with 4% paraformaldehyde at room temperature.…”

Section: Methodsmentioning

confidence: 99%

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Decellularized Human Umbilical Tissue-Derived Hydrogels Promote Proliferation and Chondrogenic Differentiation of Mesenchymal Stem Cells

Ekram

Frazier²,

Salim

et al. 2022

Bioengineering

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Tissue engineering is a promising approach for the repair and regeneration of cartilaginous tissue. Appropriate three-dimensional scaffolding materials that mimic cartilage are ideal for the repair of chondral defects. The emerging decellularized tissue-based scaffolds have the potential to provide essential biochemical signals and structural integrity, which mimics the natural tissue environment and directs cellular fate. Umbilical cord-derived hydrogels function as 3D scaffolding material, which support adherence, proliferation, migration, and differentiation of cells due to their similar biochemical composition to cartilage. Therefore, the present study aimed to establish a protocol for the formulation of a hydrogel from decellularized human umbilical cord (DUC) tissue, and assess its application in the proliferation and differentiation of UC-MSCs along chondrogenic lineage. The results showed that the umbilical cord was efficiently decellularized. Subsequently, DUC hydrogel was prepared, and in vitro chondral differentiation of MSCs seeded on the scaffold was determined. The developed protocol efficiently removed the cellular and nuclear content while retaining the extracellular matrix (ECM). DUC tissue, pre-gel, and hydrogels were evaluated by FTIR spectroscopy, which confirmed the gelation from pre-gel to hydrogel. SEM analysis revealed the fibril morphology and porosity of the DUC hydrogel. Calcein AM and Alamar blue assays confirmed the MSC survival, attachment, and proliferation in the DUC hydrogels. Following seeding of UC-MSCs in the hydrogels, they were cultured in stromal or chondrogenic media for 28 days, and the expression of chondrogenic marker genes including TGF-β1, BMP2, SOX-9, SIX-1, GDF-5, and AGGRECAN was significantly increased (* p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001). Moreover, the hydrogel concentration was found to significantly affect the expression of chondrogenic marker genes. The overall results indicate that the DUC-hydrogel is compatible with MSCs and supports their chondrogenic differentiation in vitro.

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“…Tissue processing for histological analysis was performed as previously described [ 32 , 33 ]. Briefly, native and DUC tissue were fixed with 4% paraformaldehyde at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…MSCs from human umbilical cord tissue was isolated and characterized as previously described [ 33 , 35 ]. Passage 2–5 MSCs were used for the experiments.…”

Section: Methodsmentioning

confidence: 99%

Decellularized Human Umbilical Tissue-Derived Hydrogels Promote Proliferation and Chondrogenic Differentiation of Mesenchymal Stem Cells

Ekram

Frazier²,

Salim

et al. 2022

Bioengineering

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“…Interestingly, evidence showed that the early disappearance of NC density in NP is crucial for IVD stability and induces impairment in the ECM anabolic/catabolic proportion, resulting in the change of the IVD mechanical properties[ 25 , 35 ]. IVDD is related to expanded ECM disruption[ 36 ], abnormal matrix formation[ 37 ], cellular apoptosis[ 38 ], inflammation[ 39 ], and regulation of sensory nerve and blood vessel in-growth into a normal avascular and neural tissue[ 40 ].…”

Section: Ivddmentioning

confidence: 99%

“…It has been revealed that a large number of people with no pain show degenerative disc changes that further complicate the differentiation of typical age-related degeneration from pathological conditions[ 46 ]. An increase in catabolic action of matrix-degrading proteases, pro-inflammatory cytokines, and contemporary immune cell infiltration is proposed to define disc degeneration factors[ 39 ]. Furthermore, lower disc pH, reduced nutrition, and calcified cartilaginous endplate (CEP) create an unfavorable environment for restoring the disc[ 47 ].…”

Section: Ivddmentioning

confidence: 99%

“…Approximately, 75%-90% of chronic LBP patients obtain satisfactory results with conservative treatment[ 34 , 61 ]. The pain symptoms can be overcome by administering anti-inflammatory mediators, for example, opioids, steroids, non-steroidal anti-inflammatory drugs, and muscle relaxants[ 39 ]. These anti-inflammatory drugs have effective short-term alleviation for back pain, but they cannot reverse the progression of IVDD[ 62 ].…”

Section: Therapeutics For Degenerative Intervertebral Discsmentioning

confidence: 99%

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Regulating the fate of stem cells for regenerating the intervertebral disc degeneration

Ekram¹,

Khalid²,

Salim³

et al. 2021

WJSC

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Lower back pain is a leading cause of disability and is one of the reasons for the substantial socioeconomic burden. The etiology of intervertebral disc (IVD) degeneration is complicated, and its mechanism is still not completely understood. Factors such as aging, systemic inflammation, biochemical mediators, toxic environmental factors, physical injuries, and genetic factors are involved in the progression of its pathophysiology. Currently, no therapy for restoring degenerated IVD is available except pain management, reduced physical activities, and surgical intervention. Therefore, it is imperative to establish regenerative medicine-based approaches to heal and repair the injured disc, repopulate the cell types to retain water content, synthesize extracellular matrix, and strengthen the disc to restore normal spine flexion. Cellular therapy has gained attention for IVD management as an alternative therapeutic option. In this review, we present an overview of the anatomical and molecular structure and the surrounding pathophysiology of the IVD. Modern therapeutic approaches, including proteins and growth factors, cellular and gene therapy, and cell fate regulators are reviewed. Similarly, small molecules that modulate the fate of stem cells for their differentiation into chondrocytes and notochordal cell types are highlighted.

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3D bio scaffold support osteogenic differentiation of mesenchymal stem cells

Ramzan,

Khalid,

Ekram

et al. 2024

Cell Biology International

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The regeneration of osteochondral lesions by tissue engineering techniques is challenging due to the lack of physicochemical characteristics and dual‐lineage (osteogenesis and chondrogenesis). A scaffold with better mechanical properties and dual lineage capability is required for the regeneration of osteochondral defects. In this study, a hydrogel prepared from decellularized human umbilical cord tissue was developed and evaluated for osteochondral regeneration. Mesenchymal stem cells (MSCs) isolated from the umbilical cord were seeded with hydrogel for 28 days, and cell‐hydrogel composites were cultured in basal and osteogenic media. Alizarin red staining, quantitative polymerase chain reaction, and immunofluorescent staining were used to confirm that the hydrogel was biocompatible and capable of inducing osteogenic differentiation in umbilical cord‐derived MSCs. The findings demonstrate that human MSCs differentiated into an osteogenic lineage following 28 days of cultivation in basal and osteoinductive media. The expression was higher in the cell‐hydrogel composites cultured in osteoinductive media, as evidenced by increased levels of messenger RNA and protein expression of osteogenic markers as compared to basal media cultured cell‐hydrogel composites. Additionally, calcium deposits were also observed, which provide additional evidence of osteogenic differentiation. The findings demonstrate that the hydrogel is biocompatible with MSCs and possesses osteoinductive capability in vitro. It may be potentially useful for osteochondral regeneration.

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Human umbilical cord-derived mesenchymal stem cells and their chondroprogenitor derivatives reduced pain and inflammation signaling and promote regeneration in a rat intervertebral disc degeneration model

Cited by 29 publications

References 53 publications

Decellularized Human Umbilical Tissue-Derived Hydrogels Promote Proliferation and Chondrogenic Differentiation of Mesenchymal Stem Cells

Decellularized Human Umbilical Tissue-Derived Hydrogels Promote Proliferation and Chondrogenic Differentiation of Mesenchymal Stem Cells

Regulating the fate of stem cells for regenerating the intervertebral disc degeneration

3D bio scaffold support osteogenic differentiation of mesenchymal stem cells

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