scholarly journals Experimental approach to nasal septal cartilage regeneration with adipose tissue‐derived stem cells and decellularized porcine septal cartilage

2020 ◽  
Author(s):  
Constanze Kuhlmann ◽  
Thilo Ludwig Schenck ◽  
Katharina Tluczynski ◽  
Attila Aszodi ◽  
Philipp Metzger ◽  
...  
2021 ◽  
Vol 22 (18) ◽  
pp. 9917
Author(s):  
Constanze Kuhlmann ◽  
Thilo L. Schenck ◽  
Attila Aszodi ◽  
Riccardo E. Giunta ◽  
Paul Severin Wiggenhauser

Previous anatomical studies have shown different functional zones in human nasal septal cartilage (NC). These zones differ in respect to histological architecture and biochemical composition. The aim of this study was to investigate the influence of these zones on the fate of stem cells from a regenerative perspective. Therefore, decellularized porcine septal cartilage was prepared and subjected to histological assessment to demonstrate its equivalence to human cartilage. Decellularized porcine NC (DPNC) exposed distinct surfaces depending on two different histological zones: the outer surface (OS), which is equivalent to the superficial zone, and the inner surface (IS), which is equivalent to the central zone. Human adipose tissue-derived stem cells (ASCs) were isolated from the abdominal fat tissue of five female patients and were seeded on the IS and OS of DPNC, respectively. Cell seeding efficiency (CSE), vitality, proliferation, migration, the production of sulfated glycosaminoglycans (sGAG) and chondrogenic differentiation capacity were evaluated by histological staining (DAPI, Phalloidin, Live-Dead), biochemical assays (alamarBlue®, PicoGreen®, DMMB) and the quantification of gene expression (qPCR). Results show that cell vitality and CSE were not influenced by DPNC zones. ASCs, however, showed a significantly higher proliferation and elevated expression of early chondrogenic differentiation, as well as fibrocartilage markers, on the OS. On the contrary, there was a significantly higher upregulation of hypertrophy marker MMP13 (p < 0.0001) and GAG production (p = 0.0105) on the IS, whereas cell invasion into the three-dimensional DPNC was higher in comparison to the OS. We conclude that the zonal-dependent distinct architecture and composition of NC modulates activities of ASCs seeded on DPNC. These findings might be used for engineering of cartilage substitutes needed in facial reconstructive surgery that yield an equivalent histological and functional structure, such as native NC.


Cartilage regenerative medicine has been met with much interest due to their ability to inhibit disease progression of osteoarthritis (OA). The use of adipose-derived stem cells has been suggested as a reliable method for OA treatment because of their potential to differentiate into a variety of cell lines and their potent capability to self-renewal and repair. The aim of this study is to assess adipose-derived stem cells in combination with PRP ability in treating a patient with knee OA. A 53-year- old man with osteoarthritis was selected for this treatment. Human abdominal subcutaneous adipose sample was obtained from a patient with knee OA. Stem cells were obtained from adipose tissue of abdominal origin by digesting lipoaspirate tissue with collagenase. ADSCs cultured in DMEM medium supplemented with 10% FBS. Also, ADSCs expanded and characterized by flow cytometry. These stem cells, along with platelet-rich plasma and calcium chloride, were injected into the right knee. Pre-treatment and post-treatment MRI scans, physical therapy, and pain score data were then analyzed. The MRI data for the patient demonstrated significant positive changes. Probable cartilage regeneration was sensible in the patient. Along with MRI evidence, the measured physical therapy outcomes, subjective pain, and functional status all improved. Autologous adipose-derived stem cell injection, in conjunction with platelet-rich plasma is a promising minimally invasive therapy for osteoarthritis of human knees. The present clinical case report demonstrated that a combination of percutaneous injection of autologous ADSCs and PRPmay be able to regenerate cartilage in human knee OA.


2017 ◽  
Vol 357 (2) ◽  
pp. 222-235 ◽  
Author(s):  
Marta Anna Szychlinska ◽  
Paola Castrogiovanni ◽  
Houda Nsir ◽  
Michelino Di Rosa ◽  
Claudia Guglielmino ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Jaewoo Pak ◽  
Jung Hun Lee ◽  
Wiwi Andralia Kartolo ◽  
Sang Hee Lee

Osteoarthritis (OA) is one of the most common debilitating disorders among the elderly population. At present, there is no definite cure for the underlying causes of OA. However, adipose tissue-derived stem cells (ADSCs) in the form of stromal vascular fraction (SVF) may offer an alternative at this time. ADSCs are one type of mesenchymal stem cells that have been utilized and have demonstrated an ability to regenerate cartilage. ADSCs have been shown to regenerate cartilage in a variety of animal models also. Non-culture-expanded ADSCs, in the form of SVF along with platelet rich plasma (PRP), have recently been used in humans to treat OA and other cartilage abnormalities. These ADSCs have demonstrated effectiveness without any serious side effects. However, due to regulatory issues, only ADSCs in the form of SVF are currently allowed for clinical uses in humans. Culture-expanded ADSCs, although more convenient, require clinical trials for a regulatory approval prior to uses in clinical settings. Here we present a systematic review of currently available clinical studies involving ADSCs in the form of SVF and in the culture-expanded form, with or without PRP, highlighting the clinical effectiveness and safety in treating OA.


2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Yura Lee ◽  
Yo Seph Park ◽  
Na Young Choi ◽  
Yong Il Kim ◽  
Yong-Gon Koh

Paracrine factors secreted by mesenchymal stem cells (MSCs) reportedly modulate inflammation and reparative processes in damaged tissues and have been explored for knee osteoarthritis (OA) therapy. Although various studies have reported the effects of paracrine factors in knee OA, it is not yet clear which paracrine factors directly affect the regeneration of damaged cartilage and which are secreted under various knee OA conditions. In this study, we cultured MSCs derived from three types of tissues and treated each type with IL-1β and TNF-α or not to obtain conditioned medium. Each conditioned medium was used to analyse the paracrine factors related to cartilage regeneration using liquid chromatography-tandem mass spectrometry. Bone marrow-, adipose tissue-, and synovial membrane-MSCs (all-MSCs) exhibited expression of 93 proteins under normal conditions and 105 proteins under inflammatory conditions. It was confirmed that the types of secreted proteins differed depending on the environmental conditions, and the proteins were validated using ELISA. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis using a list of proteins secreted by all-MSCs under each condition confirmed that the secreted proteins were closely related to cartilage repair under inflammatory conditions. Protein-protein interaction networks were confirmed to change depending on environmental differences and were found to enhance the secretion of paracrine factors related to cartilage regeneration under inflammatory conditions. In conclusion, our results demonstrated that compared with knee OA conditions, the differential expression proteins may contribute to the regeneration of damaged cartilage. In addition, the detailed information on commonly secreted proteins by all-MSCs provides a comprehensive basis for understanding the potential of paracrine factors to influence tissue repair and regeneration in knee OA.


2018 ◽  
Vol 19 (7) ◽  
pp. 2146 ◽  
Author(s):  
Jaewoo Pak ◽  
Jung Lee ◽  
Natalie Pak ◽  
Yoon Pak ◽  
Kwang Park ◽  
...  

Adipose tissue-derived stem cells (ASCs) in the form of stromal vascular fraction (SVF) and cultured expansion have been applied in clinical settings in some countries to treat osteoarthritis (OA) of knees, one of the most common debilitating, incurable disorders. Since the first report of successful cartilage-like tissue regeneration with autologous adipose SVF containing ASCs, there has been a gradual increase in the number of publications confirming such results. Thus far, most of the reports have been limited to treatments of OA of knees. Recently, successful applications of adipose SVF in treating OA of ankles and hips have been reported. In addition, several groups have reported modified methods of applying adipose SVF, such as combining bone marrow stimulation with adipose SVF or adding additional extracellular matrix (ECM) in treating OA. Here, we present an updated, systematic review of clinical effectiveness and safety in treating OA of knees, ankles, and one hip since 2016 using ASCs in the form of adipose SVF or in cultured expansion, along with a description and suggestion of potential biological mechanisms of cartilage regeneration.


2020 ◽  
Vol 21 (10) ◽  
pp. 3589 ◽  
Author(s):  
Daiki Murata ◽  
Ryota Fujimoto ◽  
Koichi Nakayama

Osteoarthritis (OA) is a major joint disease that promotes locomotor deficiency during the middle- to old-age, with the associated disability potentially decreasing quality of life. Recently, surgical strategies to reconstruct both articular cartilage and subchondral bone for OA have been diligently investigated for restoring joint structure and function. Adipose tissue-derived mesenchymal stem cells (AT-MSCs), which maintain pluripotency and self-proliferation ability, have recently received attention as a useful tool to regenerate osteocartilage for OA. In this review, several studies were described related to AT-MSC spheroids, with scaffold and scaffold-free three-dimensional (3D) constructs produced using “mold” or “Kenzan” methods for osteochondral regeneration. First, several examples of articular cartilage regeneration using AT-MSCs were introduced. Second, studies of osteochondral regeneration (not only cartilage but also subchondral bone) using AT-MSCs were described. Third, examples were presented wherein spheroids were produced using AT-MSCs for cartilage regeneration. Fourth, osteochondral regeneration following autologous implantation of AT-MSC scaffold-free 3D constructs, fabricated using the “mold” or “Kenzan” method, was considered. Finally, prospects of osteochondral regeneration by scaffold-free 3D constructs using AT-MSC spheroids were discussed.


2021 ◽  
Vol 14 (12) ◽  
pp. 1280
Author(s):  
Henry Yue-Hong Meng ◽  
Victor Lu ◽  
Wasim Khan

Cartilage defects are a predisposing factor for osteoarthritis. Conventional therapies are mostly palliative and there is an interest in developing newer therapies that target the disease’s progression. Mesenchymal stem cells (MSCs) have been suggested as a promising therapy to restore hyaline cartilage to cartilage defects, though the optimal cell source has remained under investigation. A PRISMA systematic review was conducted utilising five databases (MEDLINE, EMBASE, Cochrane Library, Scopus, Web of Science) which identified nineteen human studies that used adipose tissue-derived MSC (AMSC)-based therapies, including culture-expanded AMSCs and stromal vascular fraction, to treat cartilage defects. Clinical, imaging and histological outcomes, as well as other relevant details pertaining to cartilage regeneration, were extracted from each study. Pooled analysis revealed a significant improvement in WOMAC scores (mean difference: −25.52; 95%CI (−30.93, −20.10); p < 0.001), VAS scores (mean difference: −3.30; 95%CI (−3.72, −2.89); p < 0.001), KOOS scores and end point MOCART score (mean: 68.12; 95%CI (62.18, 74.05)), thus showing improvement. The studies in this review demonstrate the safety and efficacy of AMSC-based therapies for cartilage defects. Establishing standardised methods for MSC extraction and delivery, and performing studies with long follow-up should enable future high-quality research to provide the evidence needed to bring AMSC-based therapies into the market.


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