Fate of stem cell transplants in peripheral nerves

Abstract

While damaged peripheral nerves demonstrate some potential to regenerate, complete functional recovery remains infrequent, owing to a functional loss of supportive Schwann cells distal to the injury. An emerging solution to improve upon this intrinsic regenerative capacity is to supplement injured nerves with stem cells derived from various tissues. While many of these strategies have proven successful in animal models, few studies have examined the behavior of transplanted stem cells in vivo, including whether they survive and differentiate. In previous work, we demonstrated that cells derived from neonatal rodent dermis (skin-derived precursor cells, or SKPs) could improve regenerative parameters when transplanted distal to both acute and chronic nerve injuries in Lewis rats. The aim of this work was to track the fate of these cells in various nerve injury paradigms and determine the response of these cells to a known glial growth factor. Here, we report that SKPs survive, respond to local cues, differentiate into myelinating Schwann cells, and avoid complete clearance by the host's immune defenses for a minimum of 10weeks. Moreover, the ultimate fate of SKPs in vivo depends on the nerve environment into which they are injected and can be modified by inclusion of heregulin-1β.

Augmenting peripheral nerve regeneration using stem cells: A review of current opinion

“…Muscle weight and CMAPs superior in SKP-SC group in comparison to media injected controls; significantly higher counts of axon regeneration in SKP-SC group equivalent to immediate suture group Walsh et al [22] Rat sciatic transection [122] Rat sciatic and tibial (12 mm gap)…”

“…This is commonly achieved with exposure to β-mercaptoethanol, all-trans retinoic acid, fetal bovine serum, forskolin, recombinant human bFGF, recombinant human platelet derived growth factor-AA, and recombinant human heregulin β-1 [19,20] . The purported benefits of differentiation include superior in vivo viability and an enhancement of neurotrophic factor secretion and myelinating ability [14,21,22] . Many investigators have shown the beneficial effects on regeneration of these cells [19][20][21][23][24][25][26][27][28][29][30][31] .…”

“…When cultured with neuregulin-1β, rodent and human SKPs express markers consistent with functioning SCs [115][116][117][118][119][120] . Exogenous neureglins and heregulin-1β may also improve in vivo viability by reducing apoptosis [22] . Both undifferentiated and differentiated SKPs (SKP-SCs) have been shown to have positive effects on regeneration.…”

“…Both undifferentiated and differentiated SKPs (SKP-SCs) have been shown to have positive effects on regeneration. In rodent models, SKP-SCs have been shown to maintain differentiation and viability, myelinate axons, and exhibit superior outcomes following de-myelination and crush injury [117,120] , acute and chronic transection injury [22,[120][121][122] and following implantation into ANAs [122][123][124] .…”

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