Stem cell therapies for equine tendinopathy

Tendons can be injured through over-strain at a number of different sites. When injured outside a synovial cavity (extra-thecal), injuries frequently repair by fibrosis, but this tissue is functionally deficient compared to normal tendon. Stem cells offer the prospect of improving this repair to restore function and enable a successful restoration of activity while minimizing the risk of re-injury. Naturally occurring equine Superficial Digital Flexor Tendon (SDFT) overstrain injuries usually have a contained lesion, thereby enabling simple intra-tendinous injection and, by the time of stem cell implantation, is filled with granulation tissue which acts as a vascularized scaffold. An anabolic drive is provided by mechanical loading of the tendon and the suspension of mesenchymal stem cells (MSCs) in bone marrow supernatant, which we have shown to have significant anabolic effects in vitro. To test the hypothesis that stem cells will enhance tendon healing, a controlled experimental study of naturally occurring SDFT injuries (n=12) has been performed (Smith et al. 2013). MSC treatment appeared to ‘normalize’ the tissue parameters so that they were closer to the contralateral, relatively normal, and untreated tendons than saline-injected controls, in spite of labelling experiments showing the majority of cells being lost within 24 hours (Becerra et al. 2013; Sole et al. 2013). A second adequately powered and independently analyzed study evaluated the clinical outcome of naturally occurring SDFT injuries treated using this technique (n=113), which showed a significantly reduced re-injury rate (Godwin et al. 2012). Intrasynovial (intra-thecal) tendon tears usually communicate with the synovial cavity where the synovial environment is particularly challenging for successful repair. However, MSCs administered intra-synovially failed to improve healing in either equine (naturally occurring) and ovine (induced) deep digital flexor tendon (DDFT) tears (Khan et al. 2018). Labelling of the implanted cells showed them to lodge within the synovium with no cells present in the tendon defect. Scaffolds are likely to offer better advantages for enhancing repair of intra-thecal tendon tears.

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Multifunctional silica-coated iron oxide nanoparticles: a facile four-in-one system for in situ study of neural stem cell harvesting

Faraday Discussions ◽

10.1039/c4fd00132j ◽

2014 ◽

Vol 175 ◽

pp. 13-26 ◽

Cited By ~ 15

Author(s):

Yung-Kang Peng ◽

Cathy N. P. Lui ◽

Tsen-Hsuan Lin ◽

Chen Chang ◽

Pi-Tai Chou ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Iron Oxide ◽

Magnetic Resonance ◽

Neural Stem Cells ◽

Neural Stem Cell ◽

Cell Therapies ◽

Bimodal Imaging

Neural stem cells (NSCs), which generate the main phenotypes of the nervous system, are multipotent cells and are able to differentiate into multiple cell types via external stimuli from the environment. The extraction, modification and re-application of NSCs have thus attracted much attention and raised hopes for novel neural stem cell therapies and regenerative medicine. However, few studies have successfully identified the distribution of NSCs in a live brain and monitored the corresponding extraction processes both in vitro and in vivo. To address those difficulties, in this study multi-functional uniform nanoparticles comprising an iron oxide core and a functionalized silica shell (Fe3O4@SiO2(FITC)-CD133, FITC: a green emissive dye, CD133: anti-CD133 antibody) have been strategically designed and synthesized for use as probe nanocomposites that provide four-in-one functionality, i.e., magnetic agitation, dual imaging (both magnetic resonance and optical) and specific targeting. It is shown that these newly synthesized Fe3O4@SiO2(FITC)-CD133 particles have clearly demonstrated their versatility in various applications. (1) The magnetic core enables magnetic cell collection and T2 magnetic resonance imaging. (2) The fluorescent FITC embedded in the silica framework enables optical imaging. (3) CD133 anchored on the outermost surface is demonstrated to be capable of targeting neural stem cells for cell collection and bimodal imaging.

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Diabetic Retinopathy and Stem Cell Therapy

10.5772/intechopen.100812 ◽

2021 ◽

Author(s):

Sevil Kestane

Keyword(s):

Stem Cells ◽

Diabetic Retinopathy ◽

Stem Cell ◽

Cell Therapy ◽

Stem Cell Therapy ◽

Treatment Strategies ◽

Cell Therapies ◽

Long Time

This overview was evaluated by the development of diabetic retinopathy (DR) and the stem cell therapy approach. DR is a microvascular complication of diabetes mellitus, characterized by damage to the retinal blood vessels leading to progressive loss of vision. However, the pathophysiological mechanisms are complicated and not completely understood yet. The current treatment strategies have included medical, laser, intravitreal, and surgical approaches. It is known that the use of mesenchymal stem cells (MSC), which has a great potential, is promising for the treatment of many degenerative disorders, including the eye. In retinal degenerative diseases, MSCs were ameliorated retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Stem cell therapies show promise in neurodegenerative diseases. However, it is very important to know which type of stem cell will be used in which situations, the amount of stem cells to be applied, the method of application, and its physiological/neurophysiological effects. Therefore, it is of great importance to evaluate this subject physiologically. After stem cell application, its safety and efficacy should be followed for a long time. In the near future, widespread application of regenerative stem cell therapy may be a standard treatment in DR.

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022. Isolation of stem cells from embryos and adult bovine tissues

Reproduction Fertility and Development ◽

10.1071/srb05abs022 ◽

2005 ◽

Vol 17 (9) ◽

pp. 67

Author(s):

P. J. Verma ◽

K. Upton ◽

H. Mc Connell ◽

I. Vassiliev

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Es Cells ◽

Cell Types ◽

Invasive Technique ◽

Stem Cell Markers ◽

Rt Pcr ◽

Differentiation Potential ◽

Cell Therapies

The isolation of stem cells has become an area of increasing interest due to their potential uses in animal reproduction, somatic cell nuclear transfer and cell therapies. The most attractive options are the isolation of stem cells from individual embryos or adult somatic tissues. In addition, for cell therapy, the use of autologous stem cells is considered to have an advantage over heterologous cell based therapies in that immune rejection issues would be circumvented. Here we report on our attempts to isolate stem cells from both these sources in a bovine model. Bovine ES-like (bES) cells were successfully isolated from embryos and maintained in vitro for up to six passages. These cells retained the morphology characteristic of bES cells: small cytoplasmic/nuclear ratio, nuclei with multiple nucleoli, and multiple lipid inclusions in cytoplasm. bES cell colonies grew as monolayers, as islands of ES cells surrounded by trophectoderm (TE) cells. Immunohistochemical detection of SSEA-1 and SSEA-4 demonstrated expression of these markers in bES cells but not in TE cells. Further, the expression of the pluripotent markers Oct-4, Rex-1 and SSEA-1 by RT-PCR was also detected in bES cells but not in TE cells. On spontaneous differentiation, these cells were able to form a variety of cell types including beating muscle with the cells displaying a propensity to differentiate in a manner reminiscent of human ES cells. (2) We also report the isolation of putative stem cells from adult bovine skin biopsies, which express the stem cell markers Oct-4 and SSEA-1 analysed by RT-PCR and are capable of forming 3-dimensional colonies. These cells are obtained from a skin biopsy, a relatively non-invasive technique that makes them useful as donors for therapeutic applications. In summary, we have identified populations of stem cells from embryonic and adult bovine tissues, which are readily isolated. Further characterization of the differentiation potential of these cells is needed to identify the suitability of this population for use in autologous stem cell therapies.

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Effects of nicotine on the translation of stem cell therapy

Regenerative Medicine ◽

10.2217/rme-2020-0032 ◽

2020 ◽

Vol 15 (5) ◽

pp. 1679-1688

Author(s):

Alex HP Chan ◽

Ngan F Huang

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Therapy ◽

Stem Cell Therapy ◽

Therapeutic Potential ◽

Electronic Cigarettes ◽

Nicotine Exposure ◽

Cell Therapies ◽

Lifestyle Choices

Although stem cell therapy has tremendous therapeutic potential, clinical translation of stem cell therapy has yet to be fully realized. Recently, patient comorbidities and lifestyle choices have emerged to be important factors in the efficacy of stem cell therapy. Tobacco usage is an important risk factor for numerous diseases, and nicotine exposure specifically has become increasing more prevalent with the rising use of electronic cigarettes. This review describes the effects of nicotine exposure on the function of various stem cells. We place emphasis on the differential effects of nicotine exposure in vitro and as well as in preclinical models. Further research on the effects of nicotine on stem cells will deepen our understanding of how lifestyle choices can impact the outcome of stem cell therapies.

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The Application of Mesenchymal Stem Cells on Wound Repair and Regeneration

10.20944/preprints202103.0229.v1 ◽

2021 ◽

Author(s):

Bruna Lopes ◽

Patrícia Sousa ◽

Rui D. Alvites ◽

Mariana Vieira Branquinho ◽

Ana Catarina Sousa ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Wound Repair ◽

Skin Lesions ◽

Skin Regeneration ◽

Cell Therapies ◽

Clinical Impairment ◽

Cell Sources

In the past decades, regenerative medicine applied on skin lesions has been a field of constant improvement for both human and veterinary medicine. The process of healing cutaneous wound injuries implicates a well-organized cascade of molecular and biological processes. However, sometimes the normal process fails and can result in a chronic lesion. In addition, wounds are considered an increasing clinical impairment, due to the progressive ageing of the population, as well as the prevalence of concomitant diseases, such as diabetes and obesity, that represent risk aggravating factors for the development of chronic skin lesions. Stem cells regenerative potential has been recognized worldwide, including towards skin lesion repair, Tissue engineering techniques have long been successfully associated with stem cell therapies, namely the application of 3D bioprinted scaffolds. With this review we intend to explore several stem cell sources with promising aptitude towards skin regeneration, as well as different techniques used to deliver those cells and provide a supporting extracellular matrix environment, with effective outcomes. Furthermore, different studies are discussed, both in vitro and in vivo, towards their relevance in the skin regeneration field.

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Urine Cells-derived iPSCs: An Upcoming Frontier in Regenerative Medicine

Current Medicinal Chemistry ◽

10.2174/0929867328666210623142150 ◽

2021 ◽

Vol 28 ◽

Author(s):

Sanjeev Gautam ◽

Sangita Biswas ◽

Birbal Singh ◽

Ying Guo ◽

Peng Deng ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Drug Testing ◽

Diagnostic Tools ◽

Cell Therapies ◽

Non Invasive ◽

Key Issues ◽

Induced Pluripotent

: There is a momentous surge in the development of stem cell technology as a therapeutic and diagnostic tools. Stem cell-derived cells are currently used in various clinical trials. However, key issues and challenges involve the low differentiation efficiency, integration, and functioning of transplanted stem cells-derived cells. Extraction of bone marrow, adipose, or other mesenchymal stem cells (MSCs) involves invasive methods, specialized skills, and expensive technologies. Urine-derived cells, on the other hand, are obtained by non-invasive methods. Samples can be obtained repeatedly from patients of any age. Urine-derived cells are used to generate reprogrammed or induced pluripotent stem cells (iPSCs), which can be cultured, and differentiated into various types of cell lineages for biomedical investigations and drug testing in vitro or in vivo using model animals of human diseases. Urine cell-derived iPSCs (UiPSCs) have emerged as a major area of research and immense therapeutic significance. Given that preliminary preclinical studies are successful in terms of safety and as a regenerative tool, the UiPSCs will pave the way to develop and expedite various types of autologous stem cell therapies.

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Single-Cell Profiling of Coding and Noncoding Genes in Human Dopamine Neuron Differentiation

Cells ◽

10.3390/cells10010137 ◽

2021 ◽

Vol 10 (1) ◽

pp. 137

Author(s):

Fredrik Nilsson ◽

Petter Storm ◽

Edoardo Sozzi ◽

David Hidalgo Gil ◽

Marcella Birtele ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Single Cell ◽

Noncoding Rna ◽

Early Stage ◽

Cell Type ◽

Cell Type Specificity ◽

Neuron Differentiation ◽

Cell Therapies

Dopaminergic (DA) neurons derived from human pluripotent stem cells (hPSCs) represent a renewable and available source of cells useful for understanding development, developing disease models, and stem-cell therapies for Parkinson’s disease (PD). To assess the utility of stem cell cultures as an in vitro model system of human DA neurogenesis, we performed high-throughput transcriptional profiling of ~20,000 ventral midbrain (VM)-patterned stem cells at different stages of maturation using droplet-based single-cell RNA sequencing (scRNAseq). Using this dataset, we defined the cellular composition of human VM cultures at different timepoints and found high purity DA progenitor formation at an early stage of differentiation. DA neurons sharing similar molecular identities to those found in authentic DA neurons derived from human fetal VM were the major cell type after two months in culture. We also developed a bioinformatic pipeline that provided a comprehensive long noncoding RNA landscape based on temporal and cell-type specificity, which may contribute to unraveling the intricate regulatory network of coding and noncoding genes in DA neuron differentiation. Our findings serve as a valuable resource to elucidate the molecular steps of development, maturation, and function of human DA neurons, and to identify novel candidate coding and noncoding genes driving specification of progenitors into functionally mature DA neurons.

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The Application of Mesenchymal Stem Cells on Wound Repair and Regeneration

Applied Sciences ◽

10.3390/app11073000 ◽

2021 ◽

Vol 11 (7) ◽

pp. 3000

Author(s):

Bruna Lopes ◽

Patrícia Sousa ◽

Rui Alvites ◽

Mariana Branquinho ◽

Ana Sousa ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Wound Repair ◽

Three Dimensional ◽

Skin Lesions ◽

Skin Regeneration ◽

Cell Therapies ◽

Cell Sources

In the past decades, regenerative medicine applied on skin lesions has been a field of constant improvement for both human and veterinary medicine. The process of healing cutaneous wound injuries implicates a well-organized cascade of molecular and biological processes. However, sometimes the normal process fails and can result in a chronic lesion. In addition, wounds are considered an increasing clinical impairment, due to the progressive ageing of the population, as well as the prevalence of concomitant diseases, such as diabetes and obesity, that represent risk-aggravating factors for the development of chronic skin lesions. Stem cells’ regenerative potential has been recognized worldwide, including towards skin lesion repair, Tissue engineering techniques have long been successfully associated with stem cell therapies, namely the application of three-dimensional (3D) bioprinted scaffolds. With this review, we intend to explore several stem cell sources with promising aptitude towards skin regeneration, as well as different techniques used to deliver those cells and provide a supporting extracellular matrix environment, with effective outcomes. Furthermore, different studies are discussed, both in vitro and in vivo, in terms of their relevance in the skin regeneration field.

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Multiscale Stem Cell Technologies for Osteonecrosis of the Femoral Head

Stem Cells International ◽

10.1155/2019/8914569 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 4

Author(s):

Yi Wang ◽

Xibo Ma ◽

Wei Chai ◽

Jie Tian

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Femoral Head ◽

Stem Cell Therapies ◽

Cell Therapies ◽

Osteogenic Lineage ◽

Marrow Mesenchymal Stem Cells ◽

Or Gene

The last couple of decades have seen brilliant progress in stem cell therapies, including native, genetically modified, and engineered stem cells, for osteonecrosis of the femoral head (ONFH). In vitro studies evaluate the effect of endogenous or exogenous factor or gene regulation on osteogenic phenotype maintenance and/or differentiation towards osteogenic lineage. The preclinical and clinical outcomes accelerate the clinical translation. Bone marrow mesenchymal stem cells and adipose-derived stem cells have demonstrated better effects in the treatment of femoral head necrosis. Various materials have been used widely in the ONFH treatment in both preclinical and clinical trials. In a word, in vivo and multiscale efforts are expected to overcome obstacles in the approaches for treating ONFH and provide clinical relevance and commercial strategies in the future. Therefore, we will discuss the above aspects in this paper and present our opinions.

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What do we know about the neurogenic potential of different stem cell types?

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2012000700013 ◽

2012 ◽

Vol 70 (7) ◽

pp. 540-546 ◽

Cited By ~ 2

Author(s):

Guilherme Lepski

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Induced Pluripotent Stem Cells ◽

Cell Lines ◽

Pluripotent Stem Cells ◽

Large Body ◽

Cell Therapies ◽

Induced Pluripotent

Cell therapies, based on transplantation of immature cells, are being considered as a promising tool in the treatment of neurological disorders. Many efforts are being concentrated on the development of safe and effective stem cell lines. Nevertheless, the neurogenic potential of some cell lines, i.e., the ability to generate mature neurons either in vitro or in vivo, is largely unknown. Recent evidence indicate that this potential might be distinct among different cell lines, therefore limiting their broad use as replacement cells in the central nervous system. Here, we have reviewed the latest advancements regarding the electrophysiological maturation of stem cells, focusing our attention on fetal-derived-, embryonic-, and induced pluripotent stem cells. In summary, a large body of evidence supports the biological safety, high neurogenic potential, and in some diseases probable clinical efficiency related to fetal-derived cells. By contrast, reliable data regarding embryonic and induced pluripotent stem cells are still missing.

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