Recovery of motor and sensory functions using umbilical cord-derived mesenchymal stem cells in post-surgical axonotmesis of the left axillary nerve: A case report

INTRODUCTION

Axonotmesis, according to Seddon’s Classification, refers to a specific type of peripheral nerve lesion (PNL) characterized by axonal injury, but continuity and preservation of the surrounding connective tissue.^[1] The mechanism of this lesion is manifested after trauma, compression, or overstretching. The incidence of PNL after limb trauma ranges from 1.64% to 3.4%, and the most affected nerves in the upper extremity are the radial, cubital, and median nerves.^[2]

The physiopathology of axonotmesis is a result of irreversibly damaging the axon locally and similarly affecting the myelin sheath. Despite this damage, the surrounding stroma, including endoneurium and perineurium, remains unharmed [Figure 1].^[3] As a result, the nerve can regenerate the affected nerve fibers, restoring its function, while complete symptom recovery usually takes several months to a year.

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Figure 1:

Pathophysiology of axonotmesis. Local damage is found at the axon level (1), but the surrounding structures, such as endoneurium (2) and perineurium (3), remain preserved.

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Axonotmesis causes a combination of symptoms, including decreased muscle strength, sensitivity, numbness, and pain.^[4] This occurs due to damage to both motor and sensory fibers of the peripheral nerve, resulting in the total or partial loss of function in the affected area.^[2]

Treatment and prognosis for axonotmesis depend on various patient factors, including injury location, lesion severity, and time since initial damage. Physical therapy, occupational therapy, and pain management strategies are used to aid nerve function and quality of life; however, some patients display poor progress and unsatisfactory recovery.^[2]

The use of umbilical cord-derived mesenchymal stem cells (UC-MSCs) as a treatment for axonotmesis is beneficial due to their ability to encourage the regeneration and repair of damaged tissues.^[5] UC-MSCs are multipotent cells that can be extracted from various sources, including bone marrow, adipose tissue, and umbilical cord. UC-MSCs can differentiate into Schwann-like cells, promoting the growth of neurites,^[6] facilitating the repair process of a damaged nerve.^[5] Furthermore, their ability to secrete multiple bioactive molecules, such as growth factors, cytokines, and anti-inflammatory molecules, can modulate the inflammatory response at the site of injury, promote angiogenesis, and stimulate cell proliferation and differentiation.^[5,7]

Studies in both animal models and humans have shown that administering UC-MSCs to the site of a peripheral nerve injury can promote nerve fiber regeneration, improve motor and sensory function, and enhance tissue reinnervation.^[8,9] For example, Widodo et al. discovered that patients with late-onset total brachial plexus injury treated with intercostal nerve transfer and local UC-MSC injection experienced significant improvements in clinical outcomes such as emotional well-being, pain, and general health. Although no significant histological changes were observed, the clinical benefits observed in the UC-MSC group support the potential role of stem cell therapy in enhancing recovery in peripheral nerve injuries.^[10]

In this report, we present the use of expanded UC-MSCs for treating peripheral nerve injury in the axillary nerve following trauma. The Regenerative Medicine Institute’s (RMI) lab isolates, expands, and stores UC-MSCs from screened umbilical cords donated after C-sections. Cells are quality-tested, cryopreserved, and checked for viability to ensure accurate dosing before use.

CASE REPORT

A 48-year-old right-handed male microsurgeon with no prior medical history presented to a private hospital emergency department in Costa Rica with a left proximal humerus fracture sustained during a soccer game. He underwent left shoulder surgery via the Latarjet technique, using an anterior approach with a posterior arthroscopic port.

Postoperatively, the limb was immobilized for 2 weeks. At follow-up, he showed weakness in abduction, extension, and flexion. Physical therapy was recommended, including strengthening, mobilization, and electrostimulation.

At 6 weeks post-surgery [Video 1], the patient exhibited <20° of active abduction and flexion against gravity and mild resistance, with preserved extension. Lateral proximal arm paresthesia without sensory response was noted, and symptoms remained unchanged since surgery.

Nerve conduction studies revealed reduced axillary nerve amplitude and significant contralateral differences, with fibrillation (+++) and positive sharp wave (PSW) (+++) [Figure 2]. Electromyography (EMG) revealed denervation of all deltoid portions, with partial activation and reinnervation motor unit action potentials (MUAPs) in the medial and posterior heads, but no anterior activation. These findings were consistent with a high-grade nerve injury compatible with axonotmesis of the left axillary nerve.

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Figure 2:

Nerve conduction velocity studies of the patient before the surgical intervention. EMG: Electromyography, NCS: Nerve Conduction Study, IA: Insertional Activity, PAW: Positive Acute Waves, HF: High Frequency, PPP: Polyphasic Potentials, AMP: Amplitude, Dur: Duration, MUAP: Motor Unit Action Potential. Highlighted number shows the amplitude previous to the intervention.

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Due to persistent disability impacting his professional performance, alternative interventions were considered. Surgery was not indicated based on the EMG findings, and the patient preferred a conservative approach. Prior physical therapy had yielded limited improvement. Evaluation at the RMI led to the administration of perineural and intramuscular UC-MSCs injections under ultrasound guidance. A solution of 766,000 viable UC-MSCs/mL in Ringer’s Lactate (RL) was used. A total of 47 mL was injected around the brachial plexus in the supraclavicular and axillary regions, the axillary nerve tract, the shoulder, and the deltoid muscle, complete protocol available in the supplementary material [Annex 1].

In addition, a 500 mL RL intravenous infusion containing 100 million UC-MSCs was administered. No immediate complications were observed. The patient was neither immobilized nor enrolled in physical therapy and resumed normal daily activities without restrictions.

Six days post-treatment, a marked functional improvement was observed. Deltoid paresthesia persisted, but the patient achieved 120° flexion and 80° abduction (both with scapular compensation), full extension, and active movement against gravity and some resistance.

At 6 weeks, examination showed 120° flexion, 110° abduction, full extension, and minimal scapular offset. All deltoid regions contracted visibly and, as confirmed by ultrasound, showed restored sensitivity. Active movements continued against gravity and some resistance, with notable range of motion gains despite incomplete strength recovery [Supplementary material, Video 1 – post-treatment].

At 3 months, nerve conduction velocity was within normal axillary nerve amplitude. EMG showed reduced fibrillation (++), absence of PSW, instability in the anterior and posterior deltoid with neuropathic MUAP, early recruitment, and asynchronous discharge. The medial deltoid showed stable membrane activity and adequate recruitment, with no evidence of prior denervation [Figure 3]. Figure 4 outlines the clinical timeline from surgery to resolution. Throughout the 4-month follow-up period after the intervention, no adverse events were reported.

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Figure 3:

Studies of the nerve conduction velocity of the patient at 3 months after the UC MSC’s injections. EMG: Electromyography, NCS: Nerve Conduction Study, IA: Insertional Activity, PAW: Positive Acute Waves, HF: High Frequency, PPP: Polyphasic Potentials, AMP: Amplitude, Dur: Duration, MUAP: Motor Unit Action Potential.

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Figure 4:

Timeline of the events that took place starting from the patient’s fracture to the 3-month follow-up visit post-stem cell injection. EMG: Electromyography.

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DISCUSSION

This case report, which explores the administration of UCMSCs perineural and intramuscular injections as an innovative treatment for axonotmesis, demonstrates a potential approach to managing peripheral nerve injuries. Rapid and substantial improvements in muscle strength, shoulder mobility, and nerve conduction parameters were observed within 6 days, with continued progress over several weeks.

While previous studies, such as those by Li et al., have demonstrated the regenerative potential of UC-MSCs in peripheral nerve injuries, this case focuses on scenarios where surgical intervention is not pursued.^[8] The recovery timeline suggests that early administration of UC-MSCs may optimize outcomes and reduce the need for prolonged physical therapy or additional surgical procedures. These findings, consistent with those of Widodo et al., who reported significant clinical improvements in patients with late-onset total brachial plexus injury treated with UC-MSCs,^[10] also demonstrate that the administration of UC-MSCs alone resulted in clinical and functional improvements.

This report, however, is limited by its single-case design and the absence of a control or comparative intervention. Furthermore, potential confounding factors must also be acknowledged. Spontaneous recovery is possible in axonal injuries, and placebo effects cannot be excluded. However, the rapid and sustained recovery, in the absence of concurrent physical therapy or other interventions, supports the notion that UC-MSCs played a contributory role. Nonetheless, controlled trials are needed to isolate the treatment effect.

Finally, although the EMG results supported a high-grade axonal lesion, definitive differentiation between axonotmesis and neuropraxia remains challenging without histological confirmation. EMG findings suggest compatibility with axonotmesis, but this diagnosis must be interpreted within the limitations of electrodiagnostic precision. We selected Seddon’s classification given its clinical utility and the lack of histological data needed to apply Sunderland’s finer grading.

CONCLUSION

This case illustrates the potential of UC-MSCs as a transformative therapy for axonotmesis, particularly in patients who are unresponsive to conventional therapies. The rapid and significant functional recovery observed highlights the importance of advancing understanding and standardizing therapy protocols with UC-MSCs, which have demonstrated a promising capacity for peripheral nerve regeneration.