Cartilage Regeneration by Chondrogenic Induced Adult Stem Cells in Osteoarthritic Sheep Model

Ude, Chinedu C.; Sulaiman, Shamsul; Min-Hwei, Ng; Chen, Hui Cheng; Ahmad, Jamal; Yahaya, Norhamdan Mohamad; Saim, Aminuddin Bin; Idrus, Ruszymah Bt Hj

doi:10.1371/journal.pone.0098770

Cited by 84 publications

(88 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3 To our knowledge this is the first clinical controlled trial with autologous BM-SC stimulated in vivo with a single intra-articular injection for the treatment of knee OA. Our study differs from other research developed in [24][25][26][27][28][29] In humans, other studies have been performed using stem cells from different collection sites such as adipose tissue [30][31][32][33] or peripheral blood through apheresis. 34,35 Some studies include case series and clinical trials with BM mesenchymal cells; some of them administered the cells by means of surgical intervention 13,[36][37][38] and others with intra-articular injection.…”

Section: Discussionmentioning

confidence: 84%

The effect of intra‐articular injection of autologous bone marrow stem cells on pain and knee function in patients with osteoarthritis

et al. 2017

View full text Add to dashboard Cite

Aim: Management of osteoarthritis (OA) is basically symptomatic. Recently, stem cells (SC) have been used in the search for an optimum treatment. We decided to conduct a controlled clinical trial to determine if a single intra-articular injection of in vivo stimulated bone marrow SC could lead to an improvement in pain management and quality of life in patients with knee OA.Method: This was a prospective, open-label, phase I/II clinical trial to assess the safety and efficacy of a single intra-articular injection of autologous stimulated bone marrow stem cells (BM-SC) in patients with knee OA. Individuals of both genders older than 30 years with confirmed diagnosis of OA who signed informed consent were included in two groups: SC group received in vivo BM stimulation with subcutaneous administration of granulocyte colony stimulating factor (G-CSF). SC were obtained by BM aspiration and administered in a single intra-articular injection. The control group received exclusively oral acetaminophen. Visual analogue scale and Western Ontario and McMaster Universities Osteoarthritis Index scores were performed at 1 week, 1 month and 6 months in both groups. This trial was registered in ClinialTrials.gov NCT01485198.Results: A total of 61 patients were included. Socio-demographic characteristics, OA grades and initial scores were similar in both groups. The BM-SC group showed significant improvement in knee pain and quality of life during the 6-month follow-up. Conclusion:The study demonstrates feasibility and supports efficacy of a completely ambulatory procedure in treatment of knee OA.

show abstract

Section: Discussionmentioning

confidence: 84%

The effect of intra‐articular injection of autologous bone marrow stem cells on pain and knee function in patients with osteoarthritis

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Although successful fluorescent labelling of MSCs with PKH26 could be confirmed at the beginning of the organ culture study (on day 1 after seeding), the fluorescent signal could not be detected in the histological sections of the seeded cartilage explants. In contrast, other studies have previously described successful fluorescence-based detection of implanted, PKH-labelled MSCs and chondrocytes after 6 weeks (sheep) [32] or 12 weeks (mice) [31] in vivo, respectively. The exact reasons for the loss of fluorescent signal will have to be investigated in detail in future studies, but may be related to differences in the experimental condition and histological processing.…”

Section: Discussionmentioning

confidence: 99%

Chondrogenic Priming at Reduced Cell Density Enhances Cartilage Adhesion of Equine Allogeneic MSCs - a Loading Sensitive Phenomenon in an Organ Culture Study with 180 Explants

Spaas¹,

Broeckx²,

Chiers

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: Clinical results of regenerative treatments for osteoarthritis are becoming increasingly significant. However, several questions remain unanswered concerning mesenchymal stem cell (MSC) adhesion and incorporation into cartilage. Methods: To this end, peripheral blood (PB) MSCs were chondrogenically induced and/or stimulated with pulsed electromagnetic fields (PEMFs) for a brief period of time just sufficient to prime differentiation. In an organ culture study, PKH26 labelled MSCs were added at two different cell densities (0.5 x10⁶ vs 1.0 x10⁶). In total, 180 explants of six horses (30 per horse) were divided into five groups: no lesion (i), lesion alone (ii), lesion with naïve MSCs (iii), lesion with chondrogenically-induced MSCs (iv) and lesion with chondrogenically-induced and PEMF-stimulated MSCs (v). Half of the explants were mechanically loaded and compared with the unloaded equivalents. Within each circumstance, six explants were histologically evaluated at different time points (day 1, 5 and 14). Results: COMP expression was selectively increased by chondrogenic induction (p = 0.0488). PEMF stimulation (1mT for 10 minutes) further augmented COL II expression over induced values (p = 0.0405). On the other hand, MSC markers remained constant over time after induction, indicating a largely predifferentiated state. In the unloaded group, MSCs adhered to the surface in 92.6% of the explants and penetrated into 40.7% of the lesions. On the other hand, physiological loading significantly reduced surface adherence (1.9%) and lesion filling (3.7%) in all the different conditions (p < 0.0001). Remarkably, homogenous cell distribution was characteristic for chondrogenic induced MSCs (+/- PEMFs), whereas clump formation occurred in 39% of uninduced MSC treated cartilage explants. Finally, unloaded explants seeded with a moderately low density of MSCs exhibited greater lesion filling (p = 0.0022) and surface adherence (p = 0.0161) than explants seeded with higher densities of MSCs. In all cases, the overall amount of lesion filling decreased from day 5 to 14 (p = 0.0156). Conclusion: The present study demonstrates that primed chondrogenic induction of MSCs at a lower cell density without loading results in significantly enhanced and homogenous MSC adhesion and incorporation into equine cartilage.

show abstract

“…[410,411] Implantation or injection of cell-seeded scaffolds has increased tissue regeneration and led to better structural organization of the repair tissue compared to the use of a scaffold alone. [414] MSCs administered with Hyaff-11 (Hyaff-11 is a 3D fibrous membranous scaffold material composed of a benzyl ester of HA [415] ) in a sheep meniscectomy OA model resulted in a reduction of inflammation in cartilage, meniscus, and synovium and produced a reversal of fibrotic and hypertrophic tissue changes which normally occur in this model without MSC administration. [412] Intra-articular injections of MSCs in sheep OA models retards the progression of OA and promotes repair of 60 mm full thickness cartilage defects [413] and stimulates cartilage regeneration in a sheep OA model induced by complete resection of the anterior cruciate ligament and medial meniscus.…”

Section: Animal Models Of Oa Which Demonstrate the Utility Of Mscsmentioning

confidence: 99%

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

Hayes

Melrose

2019

Advanced Therapeutics

View full text Add to dashboard Cite

The aim of this study is to review developments in glycosaminoglycan and proteoglycan research relevant to cartilage repair biology and in particular the treatment of osteoarthritis (OA). Glycosaminoglycans decorate a diverse range of extracellular matrix and cell associated proteoglycans conveying structural organization and physico-chemical properties to tissues. They play key roles mediating cellular interactions with bioactive growth factors, cytokines, and morphogenetic proteins, and structural fibrillar collagens, cell interactive and extracellular matrix proteoglycans, and glycoproteins which define tissue function. Proteoglycan degradation detrimentally affects tissue functional properties. Therapeutic strategies have been developed to counter these degenerative changes. Neo-proteoglycans prepared from chondroitin sulfate or hyaluronan and hyaluronan or collagen-binding peptides emulate the interactive, water imbibing, weight bearing, and surface lubricative properties of native proteoglycans. Many neo-proteoglycans outperform native proteoglycans in terms of water imbibition, matrix stabilization, and resistance to proteolytic degradation. The biospecificity of recombinant proteoglycans however, provides precise attachment to native target molecules. Visco-supplements augmented with growth factors/therapeutic cells, hyaluronan, and lubricin (orthobiologicals) have the capacity to lubricate and protect cartilage, control inflammation, and promote cartilage repair and regeneration of early cartilage lesions and may represent a more effective therapeutic approach to the treatment of mild to moderate OA and deserve further study.Similar protective perineural net structures assembled from the lectican proteoglycan family and HA also occur in the CNS/PNS. These so called perineuronal nets are visualized by immunolocalization of MAb 1B5 (+) epitope in rat brain (e) and pericellular 1B5(+) epitope expression by isolated neurons (f). Scale bars 100 µm.

show abstract

Cartilage Regeneration by Chondrogenic Induced Adult Stem Cells in Osteoarthritic Sheep Model

Cited by 84 publications

References 27 publications

The effect of intra‐articular injection of autologous bone marrow stem cells on pain and knee function in patients with osteoarthritis

The effect of intra‐articular injection of autologous bone marrow stem cells on pain and knee function in patients with osteoarthritis

Chondrogenic Priming at Reduced Cell Density Enhances Cartilage Adhesion of Equine Allogeneic MSCs - a Loading Sensitive Phenomenon in an Organ Culture Study with 180 Explants

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

Contact Info

Product

Resources

About