Current developments in human stem cell research and clinical translation
Christine Hauskeller, Arne Manzeschke, Anja Pichl in The Matrix of Stem Cell Research, 2019
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).
Clinical Ethics
Alastair V. Campbell in Bioethics, 2017
But there is another major ethical issue currently affecting regenerative medicine. This issue can be described as ‘turning hope into hype’. Throughout the world, extravagant claims are being made for stem cell therapy, and large sums are being extracted from desperate patients, when there is virtually no evidence that safe and effective methods have been established to achieve any sort of cure or even amelioration of their condition. Part of the difficulty has been that governments have been slow to regulate this new field and have not applied the same stringent conditions of prior research and post-marketing surveillance that apply to pharmaceuticals and medical devices. Regenerative medicine does seem to hold out great hope for the future, but, for the present, the shortcomings and ethical uncertainties associated with transplantation and other proven therapies seem likely to remain.
Management of Diabetic Gastroparesis
Emmanuel C. Opara, Sam Dagogo-Jack in Nutrition and Diabetes, 2019
Prolonged survival of cells after transplantation into the gut is another necessary step for successful cell replacement therapy. Methods to increase antiapoptotic signaling, such as addition of small molecules, may be preferable to the use of gene therapy due to the hazards associated with gene therapy. The use of small molecules to inhibit pro-apoptotic factor caspase-3 has been shown to improve survival of neural stem cells transplanted into the pylorus of mice [80]. Pretreatment of cells with caspase inhibitors may be a good approach to enhance survival following in vivo transplantation.
Safranal-promoted differentiation and survival of dopaminergic neurons in an animal model of Parkinson’s disease
Published in Pharmaceutical Biology, 2018
In this study, we tried to use NSC to achieve cell-replacement therapy. According to the experimental results, we proved that NSC could directly differentiate into TH+ neurons in a neuron differentiation medium. Although the intrinsic control of dopaminergic fate specification remains to be clarified, a higher percentage of the NSC could differentiate into TH+ cells after adding SAF. By using flow cytometry and real time PCR, We observed that TH and DAT were up-regulated in the SAF group and most of cells expressed TH and DA. Furthermore, the ELISA assay also suggested TH+ cells were able to synthesis and release more DA after treatment with SAF. So far, there are several reports on the transplantation of stem cell-derived cells into PD models, but the cell survival rate is low (Love et al. 2002; Ben-Hur et al. 2004; Kriks et al. 2011). We applied intrastriatal transplantation of PD rats to test the function of our NSC in vivo. Two weeks after implantation, we found that differentiated cells survived in the brain and the number of transplanted cells was much more in the SAF group.TH positive cells presenting in the brain were also much more, indicating that SAF promoted the differentiation and survival of DA cells. However, more work should be done to achieve survival, maintenance and function of NSC in vivo.
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.
Polysaccharide-based hydrogels for drug delivery and wound management: a review
Published in Expert Opinion on Drug Delivery, 2022
Dhruv Sanjanwala, Vaishali Londhe, Rashmi Trivedi, Smita Bonde, Sujata Sawarkar, Vinita Kale, Vandana Patravale
Stem cell therapy, another type of cellular therapy, uses stem cells to treat and prevent various diseases and disorders. Biomimetic systems that can imitate native body tissues, like hydrogels, are the most suitable for the delivery of stem cells. For example, in the case of critical limb ischemia, a condition caused by severe occlusion of arteries in the limbs resulting in a significant reduction in blood supply to the extremities, pro-angiogenic stem cells have been explored as a new treatment modality. In a study by Wang and coworkers, HA/chitosan composite hydrogels with immobilized C domain peptide of the insulin-like growth factor 1 were explored as carriers for adipose derived stromal cells (proangiogenic cells). The hydrogels improved the viability and proangiogenic activity of the cells. Upon injection into murine models of ischemic hind limbs, the cell-laden hydrogels significantly improved blood perfusion and muscle regeneration, thereby saving the limb function [290]. Similarly, Zhang et al. fabricated nitric oxide (NO) releasing chitosan hydrogels loaded with human placenta derived mesenchymal cells for the treatment of hindlimb ischemia. The implantation of the hydrogel ameliorated the recovery of the functions of the hindlimbs with significant enhancement neovascularization [291].
Related Knowledge Centers
- Cord Blood
- Diabetes
- Embryonic Stem Cell
- Induced Pluripotent Stem Cell
- Somatic Cell Nuclear Transfer
- Bone Marrow
- Cardiovascular Disease
- Stem Cell
- Hematopoietic Stem Cell Transplantation
- Neurodegenerative Disease