Reduced nucleotomy-induced intervertebral disc disruption through spontaneous spheroid formation by the Low Adhesive Scaffold Collagen (LASCol)

Takeoka, Yoshiki; Yurube, Takashi; Morimoto, Katsura; Kunii, Saori; Kanda, Yutaro; Tsujimoto, Ryu; Kawakami, Yoshiyuki; Fukase, Naomasa; Takeshita, Toshiyuki; Omae, Kaoru; Kakiuchi, Yuji; Miyazaki, Shingo; Kakutani, Kenichiro; Takada, Toru; Nishida, Kotaro; Fukushima, Masanori; Kuroda, R.

doi:10.1016/j.biomaterials.2020.119781

Cited by 22 publications

(34 citation statements)

References 60 publications

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“…Several ECM-based materials, such as hyaluronan-based, alginate-based, and collagen-based ones, appear to stimulate IVD-cell metabolism, although their clinical and therapeutic strategies have not been fully addressed [ 13 ]. We managed to shed light on the effects of augmenting CSPG and HA on metabolic turnover in bNP-cells under alternating cyclic and constant HP, mimicking diurnal spinal motion.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the aforementioned cellular responses to changes in HP at high OP, approaches using biomaterials and exploiting endogenous cell populations to restore cellular properties and stimulate ECM production have gained increased attention in the field of IVD regeneration [ 13 ]. While no biomaterials are clinically approved for IVD repair, mainly due to safety concerns and unclarified repair mechanisms, we selected chondroitin sulfate proteoglycan (CSPG) and hyaluronan (HA) as candidate therapeutic materials, as they are the main components of disc and cartilage ECM.…”

Section: Introductionmentioning

confidence: 99%

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Augmented Chondroitin Sulfate Proteoglycan Has Therapeutic Potential for Intervertebral Disc Degeneration by Stimulating Anabolic Turnover in Bovine Nucleus Pulposus Cells under Changes in Hydrostatic Pressure

Takeoka

Paladugu

Kang

et al. 2021

IJMS

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Nucleus pulposus (NP) cells are exposed to changes in hydrostatic pressure (HP) and osmotic pressure within the intervertebral disc. We focused on main disc matrix components, chondroitin sulfate proteoglycan (CSPG) and hyaluronan (HA) to elucidate the capability of augmented CSPG to enhance the anabolism of bovine NP (bNP) cells under repetitive changes in HP at high osmolality. Aggrecan expression with CSPG in the absence of HP was significantly upregulated compared to the no-material control (phosphate buffer saline) under no HP at 3 days, and aggrecan expression with CSPG under HP was significantly higher than the control with HA under HP at 12 days. Collagen type I expression under no HP was significantly lower with CSPG than in controls at 3 days. Although matrix metalloproteinase 13 expression under HP was downregulated compared to no HP, it was significantly greater with HA than the control and CSPG, even under HP. Immunohistology revealed the involvement of mechanoreceptor of transient receptor potential vanilloid-4 activation under HP, suggesting an HP transduction mechanism. Addition of CSPG had anabolic and anti-fibrotic effects on bNP cells during the early culture period under no HP; furthermore, it showed synergy with dynamic HP to increase bNP-cell anabolism at later time points.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Augmented Chondroitin Sulfate Proteoglycan Has Therapeutic Potential for Intervertebral Disc Degeneration by Stimulating Anabolic Turnover in Bovine Nucleus Pulposus Cells under Changes in Hydrostatic Pressure

Takeoka

Paladugu

Kang

et al. 2021

IJMS

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“…Collagen is widely distributed in the peripheral nervous system (PNS), in the form of a network of collagen IV, glycoproteins, and proteoglycans 14 . Collagen is used in tissue reconstruction because of its superior biocompatibility and biodegradability and weak immunogenicity 15,16 . We fabricated collagen tubes as a to bridge facial nerve defects.…”

Section: Introductionmentioning

confidence: 99%

“…14 Collagen is used in tissue reconstruction because of its superior biocompatibility and biodegradability and weak immunogenicity. 15,16 We fabricated collagen tubes as a to bridge facial nerve defects. Nerve growth factor (NGF) enhances the survival and regeneration of injured peripheral nerves.…”

Section: Introductionmentioning

confidence: 99%

Nerve guidance conduit promoted peripheral nerve regeneration in rats

Long

et al. 2021

Artificial Organs

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Nerve growth factor (NGF) is important for peripheral nerve regeneration. However, its short half‐life and rapid diffusion in body fluids limit its clinical efficacy. Collagen has favorable biocompatibility and biodegradability, and weak immunogenicity. Because it possesses an NGF binding domain, we cross‐linked heparin to collagen tubes to construct nerve guidance conduits for delivering NGF. The conduits were implanted to bridge a facial nerve defect in rats. Histological and functional analyses were performed to assess the effect of the nerve guidance conduit on facial nerve regeneration. Heparin enhanced the binding of NGF to collagen while retaining its bioactivity. Also, the nerve guidance conduit significantly promoted axonal growth and Schwan cell proliferation at 12 weeks after surgery. The nerve regeneration and functional recovery outcomes using the nerve guidance conduit were similar to those of autologous nerve grafting. Therefore, the nerve guidance conduit may promote safer nerve regeneration.

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“…The in-vivo IVD degeneration study was conducted using a well-established rat tail coccygeal needle puncture (Co 6–7 and Co 7–8) model. This model is commonly used due to easy accessibility of this area in rats and reported reproducibility [ 37 ]. After 2 weeks after needle injury, we injected PBS, WJ-MSCs, or WJ-MSCs-loaded HAMC (2 × 10 4 WJ-MSCs in 1 µL + 1 µL of 1% w/v HAMC) into the degenerated disc (Co 6–7 and Co 7–8) and performed MRI at six weeks after implantation ( Figure 3 A).…”

Section: Resultsmentioning

confidence: 99%

An Injectable Hyaluronan–Methylcellulose (HAMC) Hydrogel Combined with Wharton’s Jelly-Derived Mesenchymal Stromal Cells (WJ-MSCs) Promotes Degenerative Disc Repair

Choi

Joshi

Payne

et al. 2020

IJMS

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Intervertebral disc (IVD) degeneration is one of the predominant causes of chronic low back pain (LBP), which is a leading cause of disability worldwide. Despite substantial progress in cell therapy for the treatment of IVD degeneration, significant challenges remain for clinical application. Here, we investigated the effectiveness of hyaluronan–methylcellulose (HAMC) hydrogels loaded with Wharton’s Jelly-derived mesenchymal stromal cell (WJ-MSCs) in vitro and in a rat coccygeal IVD degeneration model. Following induction of injury-induced IVD degeneration, female Sprague-Dawley rats were randomized into four groups to undergo a single intradiscal injection of the following: (1) phosphate buffered saline (PBS) vehicle, (2) HAMC, (3) WJ-MSCs (2 × 104 cells), and (4) WJ-MSCs-loaded HAMC (WJ-MSCs/HAMC) (n = 10/each group). Coccygeal discs were removed following sacrifice 6 weeks after implantation for radiologic and histologic analysis. We confirmed previous findings that encapsulation in HAMC increases the viability of WJ-MSCs for disc repair. The HAMC gel maintained significant cell viability in vitro. In addition, combined implantation of WJ-MSCs and HAMC significantly promoted degenerative disc repair compared to WJ-MSCs alone, presumably by improving nucleus pulposus cells viability and decreasing extracellular matrix degradation. Our results suggest that WJ-MSCs-loaded HAMC promotes IVD repair more effectively than cell injection alone and supports the potential clinical use of HAMC for cell delivery to arrest IVD degeneration or to promote IVD regeneration.

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Reduced nucleotomy-induced intervertebral disc disruption through spontaneous spheroid formation by the Low Adhesive Scaffold Collagen (LASCol)

Cited by 22 publications

References 60 publications

Augmented Chondroitin Sulfate Proteoglycan Has Therapeutic Potential for Intervertebral Disc Degeneration by Stimulating Anabolic Turnover in Bovine Nucleus Pulposus Cells under Changes in Hydrostatic Pressure

Augmented Chondroitin Sulfate Proteoglycan Has Therapeutic Potential for Intervertebral Disc Degeneration by Stimulating Anabolic Turnover in Bovine Nucleus Pulposus Cells under Changes in Hydrostatic Pressure

Nerve guidance conduit promoted peripheral nerve regeneration in rats

An Injectable Hyaluronan–Methylcellulose (HAMC) Hydrogel Combined with Wharton’s Jelly-Derived Mesenchymal Stromal Cells (WJ-MSCs) Promotes Degenerative Disc Repair

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