Special Issue "New Technologies Based on Stem Cell-Therapies in Regenerative Medicine and Reproductive Biology"

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: closed (15 September 2021) | Viewed by 6401

Special Issue Editor

Prof. Dr. Maciej Kurpisz
E-Mail Website
Guest Editor
Department of Reproductive Biology and Stem Cells, Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland
Interests: stem cells; anti-aging; male infertility; reproductive immunology
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Special Issue Information

Dear Colleagues,

The issue is intended to address the background of modern technology of stem cell identification in respect of optimal candidates used to treat respective diseases. This will include in vitro propagation and identification of stem cells derived from tissue reservoirs, the creation of personally tailored cells out of somatic cells through induced pluripotential state (iPS), and re-differentiation into stem cell precursor-progenitor pool, genetic modifications of stem cells to increase desired capacities as. pro-angiogenic, pro-regenerative, anti-inflammatory, anti-fibrotic genes. This would include all technicalities of genes introduction (transient versus stable gene overexpression), optimization of promoters, vectors, and imaging systems (molecular probes singular/double). Personally tailored own stem cells through iPS technology would include genetic overexpression, epigenetic strategy, mRNA (including small regulatory molecules), proteins, and small chemical molecules (methylation vs demethylation). Cell re-differentiation would include cocktails of growth factors, media components, artificial intelligence automatic systems, accelerated in vitro cell maturation (specifically in case of muscular components including skeletal muscles and heart as well as cells of central nervous system). Stem cell delivery is connected with stem cell monitoring of migratory routes and transitions including novel instrumentation of live in situ tracking systems, endoscopy, ultrasound, isotopic and non-isotopic ways of detection. Stem cell retention in target organs would require chaperones for the other accompanying stem/progenitor cells, gradient creation when using interplay of receptors with chemokine attraction molecules, adjuvating medicines provided by nanotechnological means as nanocapsules with self-degrading properties and resistant to a pro-inflammatory milieu while demonstrating stimulating properties to stem cells action. Moreover, papers that outline materials, nano-materials and scaffolds in combination with both cell retention issues as well as adaptation to microenvironment and organ specificity are welcome. We seek papers on immunomodulatory properties towards stem cell, acceptance in immunoprivileged sites as a part of protocols optimization depending on demand of target organ. Finally, we are looking for papers on organoids from the future perspective of stem cell technology and 3-D organ architecture to finish a futuristic view of organ replacement.

Prof. Dr. Maciej Kurpisz
Guest Editor

Manuscript Submission Information

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Keywords

  • Stem cell tissue reservoir
  • Personally tailored stem cell interventions
  • Stem cell genetic modifications
  • Molecular reporters and cell tracking
  • Cell delivery and organ retention
  • Nanotechnological means to support stem cells action
  • Scaffolds
  • Organoids

Published Papers (5 papers)

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Research

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Article
Improving In Vitro Culture of Human Male Fetal Germ Cells
Cells 2021, 10(8), 2033; https://doi.org/10.3390/cells10082033 - 09 Aug 2021
Cited by 2 | Viewed by 918
Abstract
Male human fetal germ cells (hFGCs) give rise to spermatogonial stem cells (SSCs), which are the adult precursors of the male gametes. Human SSCs are a promising (autologous) source of cells for male fertility preservation; however, in contrast to mouse SSCs, we are [...] Read more.
Male human fetal germ cells (hFGCs) give rise to spermatogonial stem cells (SSCs), which are the adult precursors of the male gametes. Human SSCs are a promising (autologous) source of cells for male fertility preservation; however, in contrast to mouse SSCs, we are still unable to culture them in the long term. Here, we investigated the effect of two different culture media and four substrates (laminin, gelatin, vitronectin and matrigel) in the culture of dissociated second trimester testes, enriched for hFGCs. After 6 days in culture, we quantified the presence of POU5F1 and DDX4 expressing hFGCs. We observed a pronounced difference in hFGC number in different substrates. The combination of gelatin-coated substrate and medium containing GDNF, LIF, FGF2 and EGF resulted in the highest percentage of hFGCs (10% of the total gonadal cells) after 6 days of culture. However, the vitronectin-coated substrate resulted in a comparable percentage of hFGCs regardless of the media used (3.3% of total cells in Zhou-medium and 4.8% of total cells in Shinohara-medium). We provide evidence that not only the choices of culture medium but also choices of the adequate substrate are crucial for optimizing culture protocols for male hFGCs. Optimizing culture conditions in order to improve the expansion of hFGCs will benefit the development of gametogenesis assays in vitro. Full article
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Article
Assessment of Immunological Potential of Glial Restricted Progenitor Graft In Vivo—Is Immunosuppression Mandatory?
Cells 2021, 10(7), 1804; https://doi.org/10.3390/cells10071804 - 16 Jul 2021
Cited by 3 | Viewed by 1110
Abstract
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease, causing motor neuron and skeletal muscle loss and death. One of the promising therapeutic approaches is stem cell graft application into the brain; however, an immune reaction against it creates serious limitations. This study [...] Read more.
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease, causing motor neuron and skeletal muscle loss and death. One of the promising therapeutic approaches is stem cell graft application into the brain; however, an immune reaction against it creates serious limitations. This study aimed to research the efficiency of glial restricted progenitors (GRPs) grafted into murine CNS (central nervous system) in healthy models and the SOD1G93A ALS disease model. The cellular grafts were administered in semiallogenic and allogeneic settings. To investigate the models of immune reaction against grafted GRPs, we applied three immunosuppressive/immunomodulatory regimens: preimplantation factor (PiF); Tacrolimus; and CTLA-4, MR1 co-stimulatory blockade. We tracked the cells with bioluminescence imaging (BLI) in vivo to study their survival. The immune response character was evaluated with brain tissue assays and multiplex ELISA in serum and cerebrospinal fluid (CSF). The application of immunosuppressive drugs is disputable when considering cellular transplants into the immune-privileged site/brain. However, our data revealed that semiallogenic GRP graft might survive inside murine CNS without the necessity to apply any immunomodulation or immunosuppression, whereas, in the situation of allogeneic mouse setting, the combination of CTLA-4, MR1 blockade can be considered as the best immunosuppressive option. Full article
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Article
Hair-Follicle-Associated Pluripotent (HAP) Stem Cells Can Extensively Differentiate to Tyrosine-Hydroxylase-Expressing Dopamine-Secreting Neurons
Cells 2021, 10(4), 864; https://doi.org/10.3390/cells10040864 - 10 Apr 2021
Cited by 3 | Viewed by 1157
Abstract
Hair-follicle-associated pluripotent (HAP) stem cells are located in the bulge area of hair follicles from mice and humans and have been shown to differentiate to neurons, glia, keratinocytes, smooth muscle cells, melanocytes and beating cardiac muscle cells in vitro. Subsequently, we demonstrated that [...] Read more.
Hair-follicle-associated pluripotent (HAP) stem cells are located in the bulge area of hair follicles from mice and humans and have been shown to differentiate to neurons, glia, keratinocytes, smooth muscle cells, melanocytes and beating cardiac muscle cells in vitro. Subsequently, we demonstrated that HAP stem cells could effect nerve and spinal-cord regeneration in mouse models, differentiating to Schwann cells and neurons in this process. HAP stem cells can be banked by cryopreservation and preserve their ability to differentiate. In the present study, we demonstrated that mouse HAP stem cells cultured in neural-induction medium can extensively differentiate to dopaminergic neurons, which express tyrosine hydroxylase and secrete dopamine. These results indicate that the dopaminergic neurons differentiated from HAP stem cells may be useful in the future to improve the symptoms of Parkinson’s disease in the clinic. Full article
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Article
Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects
Cells 2021, 10(3), 605; https://doi.org/10.3390/cells10030605 - 09 Mar 2021
Cited by 2 | Viewed by 987
Abstract
There is a need in plastic surgery to prepare autologous adipocytes that can be transplanted in patients to reconstruct soft tissue defects caused by tumor resection, including breast cancer, and by trauma and other diseases. Direct conversion of somatic cells into adipocytes may [...] Read more.
There is a need in plastic surgery to prepare autologous adipocytes that can be transplanted in patients to reconstruct soft tissue defects caused by tumor resection, including breast cancer, and by trauma and other diseases. Direct conversion of somatic cells into adipocytes may allow sufficient functional adipocytes to be obtained for use in regeneration therapy. Chemical libraries of 10,800 molecules were screened for the ability to induce lipid accumulation in human dermal fibroblasts (HDFs) in culture. Chemical compound-mediated directly converted adipocytes (CCCAs) were characterized by lipid staining, immunostaining, and qRT-PCR, and were also tested for adipokine secretion and glucose uptake. CCCAs were also implanted into mice to examine their distribution in vivo. STK287794 was identified as a small molecule that induced the accumulation of lipid droplets in HDFs. CCCAs expressed adipocyte-related genes, secreted adiponectin and leptin, and abundantly incorporated glucose. After implantation in mice, CCCAs resided in granulation tissue and remained adipose-like. HDFs were successfully converted into adipocytes by adding a single chemical compound, STK287794. C/EBPα and PPARγ were upregulated in STK287794-treated cells, which strongly suggests involvement of these adipocyte-related transcription factors in the chemical direct conversion. Our method may be useful for the preparation of autogenous adipocytes for transplantation therapy for soft tissue defects and fat tissue atrophy. Full article
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Review

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Review
Novel Balance Mechanism Participates in Stem Cell Therapy to Alleviate Neuropathology and Cognitive Impairment in Animal Models with Alzheimer’s Disease
Cells 2021, 10(10), 2757; https://doi.org/10.3390/cells10102757 - 15 Oct 2021
Cited by 1 | Viewed by 1348
Abstract
Stem cell therapy improves memory loss and cognitive deficits in animal models with Alzheimer’s disease. The underlying mechanism remains to be determined, but it may involve the interaction of stem cells with hippocampal cells. The transplantation of stem cells alters the pathological state [...] Read more.
Stem cell therapy improves memory loss and cognitive deficits in animal models with Alzheimer’s disease. The underlying mechanism remains to be determined, but it may involve the interaction of stem cells with hippocampal cells. The transplantation of stem cells alters the pathological state and establishes a novel balance based on multiple signaling pathways. The new balance mechanism is regulated by various autocrine and paracrine cytokines, including signal molecules that target (a) cell growth and death. Stem cell treatment stimulates neurogenesis and inhibits apoptosis, which is regulated by the crosstalk between apoptosis and autophagy—(b) Aβ and tau pathology. Aberrant Aβ plaques and neurofibrillary tau tangles are mitigated subsequent to stem cell intervention—(c) inflammation. Neuroinflammation in the lesion is relieved, which may be related to the microglial M1/M2 polarization—(d) immunoregulation. The transplanted stem cells modulate immune cells and shape the pathophysiological roles of immune-related genes such as TREM2, CR1, and CD33—(e) synaptogenesis. The functional reconstruction of synaptic connections can be promoted by stem cell therapy through multi-level signaling, such as autophagy, microglial activity, and remyelination. The regulation of new balance mechanism provides perspective and challenge for the treatment of Alzheimer’s disease. Full article
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