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Nanotechnology in Stem Cell Regenerative Therapy and Its Applications
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Stem cells can act as resources of neurons in treating central nervous system disorders with different techniques by stimulating and restoring damaged neurons. Cell replacement therapy strategies were used to treat Parkinson’s and Alzheimer’s disease (AD) (Ramakrishna et al. 2011).
Current developments in human stem cell research and clinical translation
Published in Christine Hauskeller, Arne Manzeschke, Anja Pichl, The Matrix of Stem Cell Research, 2019
Stephanie Sontag, Martin Zenke
Furthermore, cell replacement therapy is progressing into the clinics and in individual cases patients have already received iPSC-derived autologous (that is, from the patient itself) tissue transplants (Trounson and DeWitt, 2016). In 2014, a patient suffering from age-related macular degeneration (AMD) causing progressive blindness was transplanted with retinal pigment epithelium cells differentiated in vitro from iPSCs and has today almost completely re-gained eyesight (Cyranoski, 2014a; Kyodo, 2015). Until now, such examples have been rare and similar procedures – e.g. the recovery of limb movement and sensation through transplantation of spinal cord neurons, or the regeneration of heart tissue after myocardial infarction through transplantation of cardiomyocytes – were only successful in rodents and non-human primates. Despite these hurdles, such and other cell replacement therapies (e.g. transplantation of neurons for Parkinson’s disease, transplantation of encapsulated insulin-producing β-islets for diabetes type I) are in phase I or II clinical trials and are expected to be tested on larger patient cohorts in the near future (Trounson and DeWitt, 2016).
Islet Transplantation in Type 1 Diabetes: Stem Cell Research and Therapy
Published in Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Medicinal Chemistry with Pharmaceutical Product Development, 2019
The pancreas is an endocrine organ in vertebrates which is essential for glucose homeostasis via secretion of insulin by beta cells. Autoimmune diseases targeting beta cells result in lack of insulin and, in turn, diabetes mellitus. Developing stem cell replacement therapy for diabetes represents a prime research interest in order to replenish or restore the functions of lost or destroyed islet beta-cells. Considerable research grew for several years, which has discovered the ways to promote differentiation of embryonic stem cells and adult stem or progenitor cells into pancreatic beta-cell lineage. The research has indicated that endocrine and exocrine pancreatic adult progenitor cells can be a potential source of islet beta-cells. The pluripotent ESCs and mesenchymal stem cells can be differentiated with the use of spontaneous or directed differentiation protocol to generate glucose-responding islet cells. The use of ESCs is associated with ethical concerns. Stem cells or mesenchymal stem cells, as well as progenitor cells recovered from readily accessible adult tissues with no or little ethical concerns such as umbilical cord blood stem cells, adipose-derived mesenchymal stem cells, fetal and adult pancreatic duct progenitor cells, are a viable source of islet cells. These tissue-derived adult stem cells can be used in autologous fashion to avoid or minimize the immunological rejection of the transplanted beta cells. The exocrine pancreatic cells, such ductal cells and acinar cells also possess the transdifferentiation capacity to produce insulin-producing cells.
Regenerative replacement of neural cells for treatment of spinal cord injury
Published in Expert Opinion on Biological Therapy, 2021
William Brett McIntyre, Katarzyna Pieczonka, Mohamad Khazaei, Michael G. Fehlings
Current treatment options for SCI are unable to regenerate the already damaged spinal cord, and are instead aimed at mitigating further damage to the spine. As such, cell replacement therapy using NPCs represents a promising regenerative avenue for SCI because NPCs can replace the diverse cells that are damaged or lost due to injury. Nonetheless, no NPC therapies have succeeded in entering the clinic to date due to a plethora of challenges. These include the imbalance between the required proportion of the three lineages of neural cells that differentiate from the transplanted cells, the cells’ maladaptive response to the harsh injury microenvironment, and the cells’ ability to target and integrate into the correct endogenous circuitry post-transplantation. Moreover, patients with an SCI have heterogeneous pathophysiology with diverse severities and neuroanatomical deficits. Therefore, we believe that precision medicine approaches should be considered for each individual and that a universal NPC treatment should not be administered for all patients. This personalized treatment approach will successfully eradicate the challenges as well as inconsistencies, and ultimately promote the clinical translation of NPC therapies.
The Placental Growth Factor Pathway and Its Potential Role in Macular Degenerative Disease
Published in Current Eye Research, 2019
Fiona Cunningham, Tine Van Bergen, Paul Canning, Imre Lengyel, Jean H. M. Feyen, Alan W. Stitt
GA is characterised by progressive modifications of Bruch’s membrane, patchy loss of the RPE, involution of the neighbouring choriocapillaris and degeneration of photoreceptors. The precise pathological mechanisms underpinning GA remain unclear and unlike nvAMD, no adequate treatments are available, although clinical trials have or are currently investigating the potential of antioxidant therapy21, Complement system inhibition22 and choroidal reperfusion. To date, many of these trials have been unsuccessful23 and there is a pressing need for new options. To this end, a recent clinical trial has investigated RPE cell replacement therapy with promising results.24 However, the impact of an abnormal microenvironment on the health of transplanted RPE has not been addressed, and cell replacement therapies may need to be combined with compound-based therapeutics for long-term success.
Combining cell and gene therapy to advance cardiac regeneration
Published in Expert Opinion on Biological Therapy, 2018
Pina Marotta, Eleonora Cianflone, Iolanda Aquila, Carla Vicinanza, Mariangela Scalise, Fabiola Marino, Teresa Mancuso, Michele Torella, Ciro Indolfi, Daniele Torella
Despite these proof-of-principle results, autologous CSC transplantation has to be considered a personalized therapy because the very high incidence of CHF in the developed world makes it general use not affordable economically and in manpower. Furthermore, considering the time needed for harvesting and expanding the autologous CSCs, this therapy cannot and will not be available in the early post-MI when it is likely to be most effective in protecting cardiomyocytes at risks and preventing pathological remodeling, the primary cause of chronic HF. For these reasons, it is imperative to develop a therapeutic protocol, which can result in a functional and histological autologous repair triggered by a therapeutic agent that can be mass-produced and is stable, off-the-shelf, available at all times, affordable, effective, and safe. Standard allogeneic cell replacement therapy requires immunosuppression with its complications and high costs. What is needed to prevent and treat the epidemic of CHF is a therapy with the characteristics delineated above that acts through the patient’s own eCSCs triggering a physiologically meaningful histological and functional autologous myocardial repair.