Practical considerations concerning the use of stem cells for peripheral nerve repair

Abstract

<jats:p>In this review the authors intend to demonstrate the need for supplementing conventional repair of the injured nerve with alternative therapies, namely transplantation of stem or progenitor cells. Although peripheral nerves do exhibit the potential to regenerate axons and reinnervate the end organ, outcome following severe nerve injury, even after repair, remains relatively poor. This is likely because of the extensive injury zone that prevents axon outgrowth. Even if outgrowth does occur, a relatively slow growth rate of regeneration results in prolonged denervation of the distal nerve. Whereas denervated Schwann cells (SCs) are key players in the early regenerative success of peripheral nerves, protracted loss of axonal contact renders Schwann cells unreceptive for axonal regeneration. Given that denervated Schwann cells appear to become effete, one logical approach is to support the distal denervated nerve environment by replacing host cells with those derived exogenously. A number of different sources of stem/precursor cells are being explored for their potential application in the scenario of peripheral nerve injury. The most promising candidate, transplant cells are derived from easily accessible sources such as the skin, bone marrow, or adipose tissue, all of which have demonstrated the capacity to differentiate into Schwann cell–like cells. Although recent studies have shown that stem cells can act as promising and beneficial adjuncts to nerve repair, considerable optimization of these therapies will be required for their potential to be realized in a clinical setting. The authors investigate the relevance of the delivery method (both the number and differentiation state of cells) on experimental outcomes, and seek to clarify whether stem cells must survive and differentiate in the injured nerve to convey a therapeutic effect. As our laboratory uses skin-derived precursor cells (SKPCs) in various nerve injury paradigms, we relate our findings on cell fate to other published studies to demonstrate the need to quantify stem cell survival and differentiation for future studies.</jats:p>

Sensory recovery after cell therapy in peripheral nerve repair: effects of naïve and skin precursor-derived Schwann cells

“…25,29,33,34,49,55 It has been found that pre-differentiation of stem cells into the Schwann cell phenotype in vitro prior to injection results in remarkably better outcomes compared with the use of undifferentiated SKPs or mesenchymal stem cells. 16,47,48 In previous studies, we and others showed that SKPs, predifferentiated in vitro into Schwann cells (SKP-SCs), survived in vivo and promoted robust axonal regrowth both in vitro and in acute and chronic models of rodent nerve injury. 5,47,51 In the present study, we therefore moved on to assess the effects of nSC and SKP-SC therapy on the functional sensory recovery of an injured limb.…”

“…Schwann cells and their stem cell-derived counterparts may recruit into the injury site cells of other types that participate in debris clearance and tissue reconstruction and revascularization. 48,49 The major novel findings in our study are: 1) Cell therapy with the use of nSCs and SKP-SCs is highly additive to (enhances) the regrowth of IB4+ sensory neurons as well as general regeneration of NF+ axons. 2) SKP-SCs and naïve Schwann cells facilitate paw sensory recovery in the regenerating sciatic nerve in an 11-week time frame.…”

“…2,9,10,17,21,26,42 Prior in vivo experiments from our group and others show some histological improvement after stem cell/Schwann cell therapies; however, the evidence for functional peripheral nerve recovery remains limited. 16,47,48 In the present study, we aimed to evaluate the potential of SCs derived from the isogenic nerve and skin precursors for improved sensory recovery in a standard sciatic nerve transection model.…”

Advances in peripheral nerve regeneration as it relates to VCA

“…92 However, the harvest procedure is invasive, and Schwann cells require a lengthy expansion time in vitro to gain enough cells to transplant. 93 Schwann cell-based therapy has previously been limited by these complicating factors.…”

Bone as a source of organism vitality and regeneration

“…The first progeny of HSCs are multipotent progenitors that retain the ability to differentiate into all hematopoietic lineages but show a lower capacity to proliferate [59] [62] reported that mouse bone-marrow-derived cells give rise to skeletal muscle cells when transplanted into damaged mouse www.fhc.viamedica.pl muscle. Thereafter, transplanted bone marrow cells were reported to generate a wide spectrum of different cell types, including hepatocytes [63], endothelial, myocardial [64][65][66], neuronal, and glial cells [67,68]. Moreover, HSC can produce cardiac myocytes and endothelial cells [69], functional hepatocytes [70], and epithelial cells of the liver, gut, lung, and skin [71].…”