Editorial

2 pages, 170 KiB

Open AccessEditorial

Red Blood Cells in Platelet-Rich Plasma: Avoid If at All Possible

by Ashim Gupta, Nicola Maffulli and Vijay Kumar Jain

Biomedicines 2023, 11(9), 2425; https://doi.org/10.3390/biomedicines11092425 - 30 Aug 2023

Cited by 2 | Viewed by 1138

The last decade has seen a noticeable upsurge in the use of biologics, including platelet-rich plasma (PRP), for applications in musculoskeletal regenerative medicine [...] Full article

(This article belongs to the Special Issue Biologics for Bone and Soft Tissue Regeneration: What Is New, What Is True)

Research

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22 pages, 18299 KiB

Open AccessArticle

Evaluation of Cartilage Integrity Following Administration of Oral and Intraarticular Nifedipine in a Murine Model of Osteoarthritis

by Viktorija Aleksiuk, Justinas Baleisis, Gailute Kirdaite, Ilona Uzieliene, Jaroslav Denkovskij, Paulius Bernotas, Tatjana Ivaskiene, Ali Mobasheri and Eiva Bernotiene

Biomedicines 2023, 11(9), 2443; https://doi.org/10.3390/biomedicines11092443 - 01 Sep 2023

Cited by 1 | Viewed by 1048

Abstract

Osteoarthritis (OA) ranks as the prevailing type of arthritis on a global scale, for which no effective treatments are currently available. Arterial hypertension is a common comorbidity in OA patients, and antihypertensive drugs, such as nifedipine (NIF), may affect the course of OA [...] Read more.

Osteoarthritis (OA) ranks as the prevailing type of arthritis on a global scale, for which no effective treatments are currently available. Arterial hypertension is a common comorbidity in OA patients, and antihypertensive drugs, such as nifedipine (NIF), may affect the course of OA progression. The aim of this preclinical study was to determine the effect of nifedipine on healthy and OA cartilage, depending on its route of administration. In this study, we used the destabilization of medial meniscus to develop a mouse model of OA. Nifedipine was applied per os or intraarticularly (i.a.) for 8 weeks to both mice with OA and healthy animals. Serum biomarker concentrations were evaluated using the Luminex platform and alterations in the knee cartilage were graded according to OARSI histological scores and investigated immunohistochemically. Nifedipine treatment per os and i.a. exerted protective effects, as assessed by the OARSI histological scores. However, long-term nifedipine i.a. injections induced the deterioration of healthy cartilage. Lubricin, cartilage intermediate layer matrix protein (CILP), collagen type VI (COLVI), CILP, and Ki67 were upregulated by the nifedipine treatment. Serum biomarkers MMP-3, thrombospondin-4, and leptin were upregulated in the healthy groups treated with nifedipine, while only the levels of MMP-3 were significantly higher in the OA group treated with nifedipine per os compared to the untreated group. In conclusion, this study highlights the differential effects of nifedipine on cartilage integrity, depending on the route of administration and cartilage condition. Full article

(This article belongs to the Special Issue Biologics for Bone and Soft Tissue Regeneration: What Is New, What Is True)

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9 pages, 2711 KiB

Open AccessCommunication

Norisoboldine, a Natural Isoquinoline Alkaloid, Inhibits Diaphyseal Fracture Healing in Mice by Alleviating Cartilage Formation

by Wenliang Yan, Meng Shen, Kainong Sun, Shiming Li, Jingyuan Miao, Jun Wang, Jiayang Xu, Pengcheng Wen and Qian Zhang

Biomedicines 2023, 11(7), 2031; https://doi.org/10.3390/biomedicines11072031 - 19 Jul 2023

Viewed by 909

Abstract

Norisoboldine (NOR), the major isoquinoline alkaloid constituent of a Chinese traditional medicine Radix Linderae, has been demonstrated to inhibit osteoclast differentiation and improve arthritis. The aim of this study is to examine the effect of NOR on bone fracture healing and the underlying [...] Read more.

Norisoboldine (NOR), the major isoquinoline alkaloid constituent of a Chinese traditional medicine Radix Linderae, has been demonstrated to inhibit osteoclast differentiation and improve arthritis. The aim of this study is to examine the effect of NOR on bone fracture healing and the underlying mechanisms correlated with bone marrow stromal cells (BMSCs) differentiation to chondrocytes. Our results showed that NOR inhibits the tibia fracture healing process by suppressing cartilage formation, which leads to less endochondral ossification, indicated by less osterix and collage I signaling at the fracture site. Moreover, NOR significantly reduced the differentiation of primary BMSCs to chondrocytes in vitro by reducing the bone morphogenetic protein 2 (BMP2) signaling. These findings imply that NOR negatively regulates the healing of the tibial midshaft fracture, which might delay the union of the fractures and should be noticed when used in other treatments. Full article

(This article belongs to the Special Issue Biologics for Bone and Soft Tissue Regeneration: What Is New, What Is True)

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Graphical abstract

14 pages, 2766 KiB

Open AccessArticle

Factors Influencing the Yield of Progenitor Cells in Bone Marrow Aspiration Concentrate—A Retrospective Analysis of 58 Patients

by Sathish Muthu, Madhan Jeyaraman, Aditya Narula, V. R. Ravi, Avinash Gandi, Manish Khanna, Nicola Maffulli and Ashim Gupta

Biomedicines 2023, 11(3), 738; https://doi.org/10.3390/biomedicines11030738 - 01 Mar 2023

Cited by 4 | Viewed by 1749

Abstract

This study aims to identify the role of subjective factors (age, sex, and comorbidities) and procedure-specific factors (aspiration volume) in influencing the yield of progenitor cells in bone marrow aspiration concentrate (BMAC) harvested from the iliac crest. A retrospective analysis was conducted on [...] Read more.

This study aims to identify the role of subjective factors (age, sex, and comorbidities) and procedure-specific factors (aspiration volume) in influencing the yield of progenitor cells in bone marrow aspiration concentrate (BMAC) harvested from the iliac crest. A retrospective analysis was conducted on 58 patients (male:female = 31:27; mean age: 52.56 ± 18.14 years) who underwent BMAC therapy between January 2020 and June 2021. The factors analyzed include individual factors such as age, sex, and comorbid conditions, and procedural factors such as aspirate volume. The mononuclear cell (MNC) count and colony-forming unit (CFU) assay were used to assess the yield of progenitors in the aspirate. Pearson’s correlation test was performed for the age, aspirate volume, and outcome parameters, such as MNC and CFU. We used the chi-square test to analyze the role of sex and comorbidities on cellular yield. The mean volume of aspirate used for BMAC therapy was 66.65 (±17.82) mL. The mean MNC count of the BMAC was 19.94 (±16.34) × 10⁶ cells, which formed 11 (±12) CFUs. Evidence of statistically significant positive associations was noted between the CFUs developed from the BMAC and the MNC count within them (r = 0.95, p < 0.001). The sex of the individual did not play any significant role in MNC count (p = 0.092) or CFUs formed (p = 0.448). The age of the individual showed evidence of a statistically significant negative association with the MNC count (r = −0.681, p < 0.001) and CFUs (r = −0.693, p < 0.001), as did the aspiration volume with the MNC count (r = −0.740, p < 0.001) and CFUs (r = −0.629, p < 0.001). We also noted a significant reduction in the MNC count (p = 0.002) and CFUs formed (p = 0.004) when the patients presented comorbidities. Individual factors such as age, comorbid conditions, and procedure factors such as aspirate volume significantly affected the yield of progenitor cells in the BMAC. The sex of the individual did not influence the yield of progenitor cells in BMAC. Full article

(This article belongs to the Special Issue Biologics for Bone and Soft Tissue Regeneration: What Is New, What Is True)

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22 pages, 4839 KiB

Open AccessArticle

Comparative Analysis of Co-Cultured Amniotic Cell-Conditioned Media with Cell-Free Amniotic Fluid Reveals Differential Effects on Epithelial–Mesenchymal Transition and Myofibroblast Activation

by Naiyou Liu, Charles M. Bowen, Mohammadali M. Shoja, Karen Larissa Castro de Pereira, Laxmi Priya Dongur, Antonio Saad, William K. Russell, Thomas Christopher Broderick, Jeffrey H. Fair and William Samuel Fagg

Biomedicines 2022, 10(9), 2189; https://doi.org/10.3390/biomedicines10092189 - 05 Sep 2022

Cited by 4 | Viewed by 2348

Abstract

Myofibroblast activation is a cellular response elicited by a variety of physiological or pathological insults whereby cells initiate a coordinated response intended to eradicate the insult and then revert back to a basal state. However, an underlying theme in various disease states is [...] Read more.

Myofibroblast activation is a cellular response elicited by a variety of physiological or pathological insults whereby cells initiate a coordinated response intended to eradicate the insult and then revert back to a basal state. However, an underlying theme in various disease states is persistent myofibroblast activation that fails to resolve. Based on multiple observations, we hypothesized that the secreted factors harvested from co-culturing amniotic stem cells might mimic the anti-inflammatory state that cell-free amniotic fluid (AF) elicits. We optimized an amnion epithelial and amniotic fluid cell co-culture system, and tested this hypothesis in the context of myofibroblast activation. However, we discovered that co-cultured amniotic cell conditioned media (coACCM) and AF have opposing effects on myofibroblast activation: coACCM activates the epithelial–mesenchymal transition (EMT) and stimulates gene expression patterns associated with myofibroblast activation, while AF does the opposite. Intriguingly, extracellular vesicles (EVs) purified from AF are necessary and sufficient to activate EMT and inflammatory gene expression patterns, while the EV-depleted AF potently represses these responses. In summary, these data indicate that coACCM stimulates myofibroblast activation, while AF represses it. We interpret these findings to suggest that coACCM, AF, and fractionated AF represent unique biologics that elicit different cellular responses that are correlated with a wide variety of pathological states, and therefore could have broad utility in the clinic and the lab. Full article

(This article belongs to the Special Issue Biologics for Bone and Soft Tissue Regeneration: What Is New, What Is True)

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Review

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14 pages, 1129 KiB

Open AccessReview

Intra-Articular Hyaluronic Acid in Osteoarthritis and Tendinopathies: Molecular and Clinical Approaches

by Fabio Ramos Costa, Mariana Ramos Costa Marques, Vinicius Calumby Costa, Gabriel Silva Santos, Rubens Andrade Martins, Marcia da Silva Santos, Maria Helena Andrade Santana, Arulkumar Nallakumarasamy, Madhan Jeyaraman, João Vitor Bizinotto Lana and José Fábio Santos Duarte Lana

Biomedicines 2023, 11(4), 1061; https://doi.org/10.3390/biomedicines11041061 - 30 Mar 2023

Cited by 11 | Viewed by 3400

Abstract

Musculoskeletal diseases continue to rise on a global scale, causing significant socioeconomic impact and decreased quality of life. The most common disorders affecting musculoskeletal structures are osteoarthritis and tendinopathies, complicated orthopedic conditions responsible for major pain and debilitation. Intra-articular hyaluronic acid (HA) has [...] Read more.

Musculoskeletal diseases continue to rise on a global scale, causing significant socioeconomic impact and decreased quality of life. The most common disorders affecting musculoskeletal structures are osteoarthritis and tendinopathies, complicated orthopedic conditions responsible for major pain and debilitation. Intra-articular hyaluronic acid (HA) has been a safe, effective, and minimally invasive therapeutic tool for treating these diseases. Several studies from bedside to clinical practice reveal the multiple benefits of HA such as lubrication, anti-inflammation, and stimulation of cellular activity associated with proliferation, differentiation, migration, and secretion of additional molecules. Collectively, these effects have demonstrated positive outcomes that assist in the regeneration of chondral and tendinous tissues which are otherwise destroyed by the predominant catabolic and inflammatory conditions seen in tissue injury. The literature describes the physicochemical, mechanical, and biological properties of HA, their commercial product types, and clinical applications individually, while their interfaces are seldom reported. Our review addresses the frontiers of basic sciences, products, and clinical approaches. It provides physicians with a better understanding of the boundaries between the processes that lead to diseases, the molecular mechanisms that contribute to tissue repair, and the benefits of the HA types for a conscientious choice. In addition, it points out the current needs for the treatments. Full article

(This article belongs to the Special Issue Biologics for Bone and Soft Tissue Regeneration: What Is New, What Is True)

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18 pages, 2472 KiB

Open AccessReview

Cell-Free Amniotic Fluid and Regenerative Medicine: Current Applications and Future Opportunities

by Charles M. Bowen, Frederick S. Ditmars, Ashim Gupta, Jo-Anna Reems and William Samuel Fagg

Biomedicines 2022, 10(11), 2960; https://doi.org/10.3390/biomedicines10112960 - 17 Nov 2022

Cited by 2 | Viewed by 2975

Abstract

Amniotic fluid (AF) provides critical biological and physical support for the developing fetus. While AF is an excellent source of progenitor cells with regenerative properties, recent investigations indicate that cell-free AF (cfAF), which consists of its soluble components and extracellular vesicles, can also [...] Read more.

Amniotic fluid (AF) provides critical biological and physical support for the developing fetus. While AF is an excellent source of progenitor cells with regenerative properties, recent investigations indicate that cell-free AF (cfAF), which consists of its soluble components and extracellular vesicles, can also stimulate regenerative and reparative activities. This review summarizes published fundamental, translational, and clinical investigations into the biological activity and potential use of cfAF as a therapeutic agent. Recurring themes emerge from these studies, which indicate that cfAF can confer immunomodulatory, anti-inflammatory, and pro-growth characteristics to the target cells/tissue with which they come into contact. Another common observation is that cfAF seems to promote a return of cells/tissue to a homeostatic resting state when applied to a model of cell stress or disease. The precise mechanisms through which these effects are mediated have not been entirely defined, but it is clear that cfAF can safely and effectively treat cutaneous wounds and perhaps orthopedic degenerative conditions. Additional applications are currently being investigated, but require further study to dissect the fundamental mechanisms through which its regenerative effects are mediated. By doing so, rational design can be used to fully unlock its potential in the biotechnology lab and in the clinic. Full article

(This article belongs to the Special Issue Biologics for Bone and Soft Tissue Regeneration: What Is New, What Is True)

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Other

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18 pages, 643 KiB

Open AccessSystematic Review

Allogenic Perinatal Tissue for Musculoskeletal Regenerative Medicine Applications: A Systematic Review

by Adarsh Aratikatla, Nicola Maffulli, Hugo C. Rodriguez, Manu Gupta, Anish G. Potty and Ashim Gupta

Biomedicines 2022, 10(12), 3173; https://doi.org/10.3390/biomedicines10123173 - 07 Dec 2022

Cited by 10 | Viewed by 1580

Abstract

Producing tremendous amounts of stress and financial burden on the global patient population and healthcare systems around the world, most current modalities of treatment for musculoskeletal ailments often do not address the etiopathogenetic causes of these disorders. Regenerative medicine for musculoskeletal disorders relies [...] Read more.

Producing tremendous amounts of stress and financial burden on the global patient population and healthcare systems around the world, most current modalities of treatment for musculoskeletal ailments often do not address the etiopathogenetic causes of these disorders. Regenerative medicine for musculoskeletal disorders relies on orthobiologics derived from either allogenic or autologous sources. Multiple drawbacks are associated with autologous sources, including donor-site morbidity, a dearth of studies, and variability in both patient reported and clinical/functional outcomes. On the other hand, allogenic sources address several of these concerns, and continue to be a suitable source of mesenchymal stem cells (MSCs). This review qualitatively reports both the preclinical and clinical outcomes of publications studying the applications of umbilical cord (-derived Wharton’s jelly), amniotic suspension allograft, amniotic membrane, and amniotic fluid in musculoskeletal medicine. A systematic review was conducted utilizing the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines on studies published between January 2010 and October 2022 that used allogeneic perinatal tissues. Further randomized controlled clinical studies are necessary to properly evaluate the safety and efficacy of these tissues in orthopedic surgery. Full article

(This article belongs to the Special Issue Biologics for Bone and Soft Tissue Regeneration: What Is New, What Is True)

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