Types of Stem Cells in Regenerative Medicine: A Review

Two basic and clinical researches accomplished during the recent years on embryonic and adult stem cells constituted a mutation in regenerative therapy. These cells can be used for treating some degenerative diseases. Between them, age-related functional defects, hematopoietic and immune system disorders, heart failures, chronic liver injuries, diabetes, Parkinson’s and Alzheimer’s diseases, arthritis and muscular, skin, lung, eye, and digestive disorders, aggressive and regressive cancers can be treated by cell therapies. This review focused on types of stem cells used in regenerative medicine

Selective laser melting–enabled electrospinning: Introducing complexity within electrospun membranes

Additive manufacturing technologies enable the creation of very precise and well-defined structures that can mimic hierarchical features of natural tissues. In this article, we describe the development of a manufacturing technology platform to produce innovative biodegradable membranes that are enhanced with controlled microenvironments produced via a combination of selective laser melting techniques and conventional electrospinning. This work underpins the manufacture of a new generation of biomaterial devices that have significant potential for use as both basic research tools and components of therapeutic implants. The membranes were successfully manufactured and a total of three microenvironment designs (niches) were chosen for thorough characterisation. Scanning electron microscopy analysis demonstrated differences in fibre diameters within different areas of the niche structures as well as differences in fibre density. We also showed the potential of using the microfabricated membranes for supporting mesenchymal stromal cell culture and proliferation. We demonstrated that mesenchymal stromal cells grow and populate the membranes penetrating within the niche-like structures. These findings demonstrate the creation of a very versatile tool that can be used in a variety of tissue regeneration applications including bone healing

Phenotypic Characterization, Osteoblastic Differentiation, and Bone Regeneration Capacity of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells

To enhance the understanding of differentiation patterns and bone formation capacity of hESCs, we determined (1) the temporal pattern of osteoblastic differentiation of human embryonic stem cell derived mesenchymal stem cells (hESC-MSCs), (2) the influence of a three-dimensional matrix on the osteogenic differentiation of hESC-MSCs in long-term culture, and (3) the bone-forming capacity of osteoblast-like cells derived from hESC-MSCs in calvarial defects. Incubation of hESC-MSCs in osteogenic medium induced osteoblastic differentiation of hESC-MSCs into mature osteoblasts in a similar chronological pattern to human bone marrow stromal cells and primary osteoblasts. Osteogenic differentiation was enhanced by culturing the cells on three-dimensional collagen scaffolds. Fluorescent-activated cell sorting of alkaline phosphatase expressing cells was used to obtain an enriched osteogenic cell population for in vivo transplantation. The identification of green fluorescence protein and expression of human-specific nuclear antigen in osteocytes in newly formed bone verified the role of transplanted human cells in the bone regeneration process. The current cell culture model and osteogenic cell enrichment method could provide large numbers of osteoprogenitor cells for analysis of differentiation patterns and cell transplantation to regenerate skeletal defects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78154/1/scd.2008.0310.pd

Microcalcifications in breast cancer: novel insights into the molecular mechanism and functional consequence of mammary mineralisation.

BACKGROUND: Mammographic microcalcifications represent one of the most reliable features of nonpalpable breast cancer yet remain largely unexplored and poorly understood. METHODS: We report a novel model to investigate the in vitro mineralisation potential of a panel of mammary cell lines. Primary mammary tumours were produced by implanting tumourigenic cells into the mammary fat pads of female BALB/c mice. RESULTS: Hydroxyapatite (HA) was deposited only by the tumourigenic cell lines, indicating mineralisation potential may be associated with cell phenotype in this in vitro model. We propose a mechanism for mammary mineralisation, which suggests that the balance between enhancers and inhibitors of physiological mineralisation are disrupted. Inhibition of alkaline phosphatase and phosphate transport prevented mineralisation, demonstrating that mineralisation is an active cell-mediated process. Hydroxyapatite was found to enhance in vitro tumour cell migration, while calcium oxalate had no effect, highlighting potential consequences of calcium deposition. In addition, HA was also deposited in primary mammary tumours produced by implanting the tumourigenic cells into the mammary fat pads of female BALB/c mice. CONCLUSION: This work indicates that formation of mammary HA is a cell-specific regulated process, which creates an osteomimetic niche potentially enhancing breast tumour progression. Our findings point to the cells mineralisation potential and the microenvironment regulating it, as a significant feature of breast tumour development

Mapping regional implementation of ‘Making Every Contact Count’: mixed-methods evaluation of implementation stage, strategies, barriers and facilitators of implementation

\ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.Background The Making Every Contact Count (MECC) programme provides training and materials to support public-facing workers to encourage health-promoting behaviour change by using the day-to-day interactions between organisations and individuals. This project aimed to analyse MECC implementation through a comparative analysis of implementation stage, strategies used for implementation and enablers/barriers of the implementation process within a region in England—the North East and North Cumbria (NENC). Methods A mixed-methods process evaluation was conducted applying normalisation process theory and theoretical domains framework. MECC programme documents were reviewed and mapped against specific criteria (eg, implementation strategies). An online mapping survey was conducted to establish current implementation/delivery of MECC within NENC settings (eg, local government, healthcare and voluntary community sector). Qualitative research, using individual interviews and group discussions, was conducted to establish further understanding of MECC implementation. Results Our findings were informed by reviewing documents (n=5), surveying participants (n=34), interviews (n=18) and group discussions (n=48). Overall, the implementation of MECC within the region was at an early stage, with training mostly delivered between, rather than within, organisations. Qualitative findings highlighted factors that influence stakeholders to implement MECC (eg, organisational goals that were facilitated by MECC implementation, including the prevention agenda), supported resources that facilitate the implementation of MECC (eg, logic models) and enabling factors that promote MECC sustainability across the region (eg, buy-in from leadership and management). Conclusions The NENC MECC programme is built around regional leadership that supports the implementation process. This process evaluation identified key influences of MECC implementation across the region. We discuss evidence-based recommendation for policy and practice that can be taken forward to develop targeted strategies to support future MECC implementation. For example, a coordinated infrastructure and strategy is needed to combat delivery and implementation issues identified

Intervention design for artificial intelligence-enabled macular service implementation: a primary qualitative study

\ua9 The Author(s) 2024. Background: Neovascular age-related macular degeneration (nAMD) is one of the largest single-disease contributors to hospital outpatient appointments. Challenges in finding the clinical capacity to meet this demand can lead to sight-threatening delays in the macular services that provide treatment. Clinical artificial intelligence (AI) technologies pose one opportunity to rebalance demand and capacity in macular services. However, there is a lack of evidence to guide early-adopters seeking to use AI as a solution to demand-capacity imbalance. This study aims to provide guidance for these early adopters on how AI-enabled macular services may best be implemented by exploring what will influence the outcome of AI implementation and why. Methods: Thirty-six semi-structured interviews were conducted with participants. Data were analysed with the Nonadoption, Abandonment, Scale-up, Spread and Sustainability (NASSS) framework to identify factors likely to influence implementation outcomes. These factors and the primary data then underwent a secondary analysis using the Fit between Individuals, Technology and Task (FITT) framework to propose an actionable intervention. Results: nAMD treatment should be initiated at face-to-face appointments with clinicians who recommend year-long periods of AI-enabled scheduling of treatments. This aims to maintain or enhance the quality of patient communication, whilst reducing consultation frequency. Appropriately trained photographers should take on the additional roles of inputting retinal imaging into the AI device and overseeing its communication to clinical colleagues, while ophthalmologists assume clinical oversight and consultation roles. Interoperability to facilitate this intervention would best be served by imaging equipment that can send images to the cloud securely for analysis by AI tools. Picture Archiving and Communication Software (PACS) should have the capability to output directly into electronic medical records (EMR) familiar to clinical and administrative staff. Conclusion: There are many enablers to implementation and few of the remaining barriers relate directly to the AI technology itself. The proposed intervention requires local tailoring and prospective evaluation but can support early adopters in optimising the chances of success from initial efforts to implement AI-enabled macular services. Protocol registration: Hogg HDJ, Brittain K, Teare D, Talks J, Balaskas K, Keane P, Maniatopoulos G. Safety and efficacy of an artificial intelligence-enabled decision tool for treatment decisions in neovascular age-related macular degeneration and an exploration of clinical pathway integration and implementation: protocol for a multi-methods validation study. BMJ Open. 2023 Feb 1;13(2):e069443. https://doi.org/10.1136/bmjopen-2022-069443. PMID: 36725098; PMCID: PMC9896175

Treatment of osteonecrosis of the femoral head using autologous cultured osteoblasts: a case report

<p>Abstract</p> <p>Introduction</p> <p>Osteonecrosis of the femoral head is a progressive disease that leads to femoral head collapse and osteoarthritis. Our goal in treating osteonecrosis is to preserve, not to replace, the femoral head.</p> <p>Case presentation</p> <p>We present the case of a patient with bilateral osteonecrosis of the femoral head treated with autologous cultured osteoblast injection.</p> <p>Conclusion</p> <p>Although our experience is limited to one patient, autologous cultured osteoblast transplantation appears to be effective for treating the osteonecrosis of femoral head.</p

Target Product Profile for a Machine Learning–Automated Retinal Imaging Analysis Software for Use in English Diabetic Eye Screening: Protocol for a Mixed Methods Study

\ua9 2024 JMIR Publications Inc.. All rights reserved.Background: Diabetic eye screening (DES) represents a significant opportunity for the application of machine learning (ML) technologies, which may improve clinical and service outcomes. However, successful integration of ML into DES requires careful product development, evaluation, and implementation. Target product profiles (TPPs) summarize the requirements necessary for successful implementation so these can guide product development and evaluation. Objective: This study aims to produce a TPP for an ML-automated retinal imaging analysis software (ML-ARIAS) system for use in DES in England. Methods: This work will consist of 3 phases. Phase 1 will establish the characteristics to be addressed in the TPP. A list of candidate characteristics will be generated from the following sources: an overview of systematic reviews of diagnostic test TPPs; a systematic review of digital health TPPs; and the National Institute for Health and Care Excellence’s Evidence Standards Framework for Digital Health Technologies. The list of characteristics will be refined and validated by a study advisory group (SAG) made up of representatives from key stakeholders in DES. This includes people with diabetes; health care professionals; health care managers and leaders; and regulators and policy makers. In phase 2, specifications for these characteristics will be drafted following a series of semistructured interviews with participants from these stakeholder groups. Data collected from these interviews will be analyzed using the shortlist of characteristics as a framework, after which specifications will be drafted to create a draft TPP. Following approval by the SAG, in phase 3, the draft will enter an internet-based Delphi consensus study with participants sought from the groups previously identified, as well as ML-ARIAS developers, to ensure feasibility. Participants will be invited to score characteristic and specification pairs on a scale from “definitely exclude” to “definitely include,” and suggest edits. The document will be iterated between rounds based on participants’ feedback. Feedback on the draft document will be sought from a group of ML-ARIAS developers before its final contents are agreed upon in an in-person consensus meeting. At this meeting, representatives from the stakeholder groups previously identified (minus ML-ARIAS developers, to avoid bias) will be presented with the Delphi results and feedback of the user group and asked to agree on the final contents by vote. Results: Phase 1 was completed in November 2023. Phase 2 is underway and expected to finish in March 2024. Phase 3 is expected to be complete in July 2024. Conclusions: The multistakeholder development of a TPP for an ML-ARIAS for use in DES in England will help developers produce tools that serve the needs of patients, health care providers, and their staff. The TPP development process will also provide methods and a template to produce similar documents in other disease areas

Ectopic bone formation in cell-seeded poly(ethylene oxide)/poly(butylene terephthalate) copolymer scaffolds of varying porosity

Scaffolds from poly(ethylene oxide) and poly(butylene terephthalate), PEOT/PBT, with a PEO molecular weight of 1,000 and a PEOT content of 70 weight% (1000PEOT70PBT30) were prepared by leaching salt particles (425–500 μm). Scaffolds of 73.5, 80.6 and 85.0% porosity were treated with a CO2 gas plasma and seeded with rat bone marrow stromal cells (BMSCs). After in vitro culture for 7 days (d) in an osteogenic medium the scaffolds were subcutaneously implanted for 4 weeks in nude mice. Poly(d, l-lactide) (PDLLA) and biphasic calcium phosphate (BCP) scaffolds were included as references. After 4 weeks (wks) all scaffolds showed ectopic formation of bone and bone marrow. For the scaffolds of different porosities, no significant differences were observed in the relative amounts of bone (7–9%) and bone marrow (6–11%) formed, even though micro computed tomography (μ-CT) data showed considerable differences in accessible pore volume and surface area. 1000PEOT70PBT30 scaffolds with a porosity of 85% could not maintain their original shape in vivo. Surprisingly, 1000PEOT70PBT30 scaffolds with a porosity of 73.5% showed cartilage formation. This cartilage formation is most likely due to poorly accessible pores in the scaffolds, as was observed in histological sections. μ-CT data showed a considerably smaller accessible pore volume (as a fraction of the total volume) than in 1000PEOT70PBT30 scaffolds of 80.6 and 85.0% porosity. BMSC seeded PDLLA (83.5% porosity) and BCP scaffolds (29% porosity) always showed considerably more bone and bone marrow formation (bone marrow formation is approximately 40%) and less fibrous tissue ingrowth than the 1000PEOT70PBT30 scaffolds. The scaffold material itself can be of great influence. In more hydrophobic and rigid scaffolds like the PDLLA or BCP scaffolds, the accessibility of the pore structure is more likely to be preserved under the prevailing physiological conditions than in the case of hydrophilic 1000PEOT70PBT30 scaffolds. Scaffolds prepared from other PEOT/PBT polymer compositions, might prove to be more suited

The behavior of osteoblast-like cells on various substrates with functional blocking of integrin-β1 and integrin-β3

This study was designed to examine the influence of integrin subunit-β1 and subunit-β3 on the behavior of primary osteoblast-like cells, cultured on calcium phosphate (CaP)-coated and non coated titanium (Ti). Osteoblast-like cells were incubated with specific monoclonal antibodies against integrin-β1 and integrin-β3 to block the integrin function. Subsequently, cells were seeded on Ti discs, either non coated or provided with a 2 μm carbonated hydroxyapatite coating using Electrostatic Spray Deposition. Results showed that on CaP coatings, cellular attachment was decreased after a pre-treatment with either anti-integrin-β1 or anti-integrin-β3 antibodies. On Ti, cell adhesion was only slightly affected after a pre-treatment with anti-integrin-β3 antibodies. Scanning electron microscopy showed that on both types of substrate, cellular morphology was not changed after a pre-treatment with either antibody. With quantitative PCR, it was shown for both substrates that mRNA expression of integrin-β1 was increased after a pre-treatment with either anti-integrin-β1 or anti-integrin-β3 antibodies. Furthermore, after a pre-treatment with either antibody, mRNA expression of integrin-β3 and ALP was decreased, on both types of substrate. In conclusion, osteoblast-like cells have the ability to compensate to great extent for the blocking strategy as applied here. Still, integrin-β1 and β3 seem to play different roles in attachment, proliferation, and differentiation of osteoblast-like cells, and responses on CaP-coated substrates differ to non coated Ti. Furthermore, the influence on ALP expression suggests involvement of both integrin subunits in signal transduction for cellular differentiation