Busting the myth: More good than harm in transgenic cells

PIÑERO, GONZALO; SETTON-AVRUJ PATRICIA

NEURAL REGENERATION RESEARCH

SHENYANG EDITORIAL DEPT NEURAL REGENERATION RES

Lugar: Filadelfia; Año: 2019 vol. 14 p. 967 - 968

1673-5374

Peripheral neuropathy constitutes a highly incidental condition and a major public health concern worldwide (Hanewinckel et al., 2016). This pathology is triggered by peripheral nervous system damage as a consequence of systemic disease or ischemic-traumatic lesion. In the latter case, nerve crush, partial or total transection and stretch injury interrupt nerve conduction and impair sensitivity and motility of the innervated area, which brings about partial or total functional loss in the affected limb and disabling neuropathic pain. For these reasons, digging into the molecular mechanisms underlying peripheral neuropathy becomes essential for the development of successful therapeutic strategies.In addition to a wide variety of animal models available for basic research and pre-clinical studies of peripheral nerve injuries, cell transplantation techniques have received a great deal of attention in recent years and have shed light on potential neuroregenerative pharmacological and cell therapies (Faroni et al., 2015), in models such as sciatic, facial or optic nerve lesions and diabetic neuropathy. In particular, the sciatic nerve crush model is widely used as an interesting approach to Wallerian degeneration (WD) with numerous advantages. This pathophysiological process is characterized by the loss of axon-Schwann cell (SC) contact, which triggers SC dedifferentiation and proliferation. This event is followed by myelin breakdown, recently found to be an autophagic process, and an inflammatory response which includes hematogenous macrophage influx participating in myelin debris removal and tissue remodeling. These constitute essential steps for the onset of axonal regeneration and remyelination (Klein and Martini, 2016).Despite the advances in cell therapy, cell tracking continues to pose an obstacle in the appraisal of transplantation results which can be partly bypassed in different ways. First, the use of cell trackers to label the population of cells to be transplanted allows for easy though short-lived staining. Second, cell transfection with plasmid coding for fluorescent proteins enables longer-lasting tracking but renders low yields. Third, cell lines are easily maintained but, in having been genetically modified, they fail to match primary cell reliability and functionality. In other words, results obtained using transgenic cell lines always need corroboration through primary cell cultures or in vivo studies. As a fourth option, transgenic animals provide more viable and reliable cells to use in vivo, both for cell tracking and functional effects. Even if these animals are more difficult and costly to maintain, as their breeding requires animal facilities and raises ethical concerns in animal care, their cells allow more sustained expression of reporter genes upon transplantation (Li et al., 2016; Pinero et al., 2018).