Effect of Systemic Adipose-derived Stem Cell Therapy on Functional Nerve Regeneration in a Rodent Model

Abstract

Background: Regardless of etiology, peripheral nerve injuries (PNI) result in disruption/loss of neuromuscular junctions, target muscle denervation, and poor sensorimotor outcomes with associated pain and disability. Adipose-derived stem cells (ASCs) have shown promise in neuroregeneration. However, there is a paucity of objective assessments reflective of functional neuroregeneration in experimental PNI. Here, we use a multimodal, static, and dynamic approach to evaluate functional outcomes after ASC therapy in a rodent PNI model. Methods: Lewis rats were divided into 3 groups: 10 mm sciatic nerve resection (“CUT” group; n = 10), transection and repair (“REP” group; n = 10), transection and repair plus single-dose ASCs (“ASC” group; n = 12). Allogeneic (Brown Norway rat) ASCs (1 × 106) were administered intravenously on postoperative day 1. Functional outcome was assessed by static sciatic index, toe spread factor, and a dynamic swim test on a weekly basis for 6 weeks. Sciatic nerves and gastrocnemius muscles were harvested at endpoint (6 weeks) for histological analysis. Results: The ASC group showed accelerated functional recovery on the swim test at 2 weeks postoperatively, with continued improvement over 4 weeks, culminating in superior overall outcomes at 6 weeks compared with the REP group. The CUT group showed no significant improvement from baseline. Nerve histomorphometry correlated well with the swim test results in the ASC group. Gastrocnemius muscle weights showed no difference between the REP and the ASC groups. Conclusion: Our study confirms that early, single dose, systemic administration of ASC after PNI accelerates and enhances overall motor recovery on static and dynamic functional tests as evidenced by improvements in voluntary as well as involuntary motions.

Role of stem cells-based in facial nerve reanimation: A meta-analysis of histological and neurophysiological outcomes

“…These treatments have demonstrated several advantages with regards to nerve fiber spreading, myelinization, and regeneration of the optimal perineural environment, thus tending to reduce fibrosis and inflammatory-mediated disorders[ 7 - 9 , 18 ]. Adipose tissue has been used in peripheral nerve reconstruction after sciatic nerve transection in animal models, which seemed to provide relevant advantages in terms of nerve fiber density, axon area, and myelin area[ 19 ]. It is important, however, to demonstrate that histology translates to functional benefits, which was investigated by Schweizer et al [ 19 ] and Tuncel et al [ 20 ], using a swim test and a walking track analysis, respectively, thus confirming clinical effectiveness.…”

“…Adipose tissue has been used in peripheral nerve reconstruction after sciatic nerve transection in animal models, which seemed to provide relevant advantages in terms of nerve fiber density, axon area, and myelin area[ 19 ]. It is important, however, to demonstrate that histology translates to functional benefits, which was investigated by Schweizer et al [ 19 ] and Tuncel et al [ 20 ], using a swim test and a walking track analysis, respectively, thus confirming clinical effectiveness.…”

Early Intensive Neurorehabilitation in Traumatic Peripheral Nerve Injury—State of the Art

“…Experimental research advancements in peripheral nerve regeneration, such as computerized video analysis, enable us to record footprints, walking patterns and bodyweight distribution, revealing the applicability of several parameters for locomotion evaluation [ 60 ]. Also, Schweizer et al (2020) [ 61 ], in rodents, introduced an alternative approach to assess functional outcomes in sciatic damage and repair after the implementation of stem cells based on the swim test [ 62 ].…”

Adipose Tissue Uses in Peripheral Nerve Surgery

“…Surgical coaptation of the transected nerve ends can help to prevent errors in reinnervation, but still requires guidance from the Schwann cells to heal the nerve after coaptation. Even then, only around 10% of axons reach the intended target muscle or organ after surgical repair following transection [ 33 ]. Nerve transections are associated with poor outcomes even after repair, especially when the distance between the nerve and target is long or when repair is performed after a delayed period [ 34 ].…”

“…Another study evaluated the functional recovery of rat sciatic nerves after repair with and without ADSCs. A swim test revealed accelerated functional recovery at 2 weeks, with continued improvement at 6 weeks, for ADSC-treated repairs compared to non-treated repairs [ 33 ]. Upon histological analysis, the ADSC-injected group had significantly higher mean values for nerve fiber density, axon area, and myelin area [ 33 ].…”