How to Use Stem Cells in Clinical Laminitis Cases

Stem cell therapy as an adjunctive treatment of laminitis in clinical cases has shown promise. In our experience, the use of stem cells in the laminitic patient prior to the development of hyperplastic undifferentiated lamella or the “lamellar wedge” has been clinically beneficial. The use of stem cells does not eliminate the need for traditional supportive care of laminitic patients. Authors’ address: Rood & Riddle Equine Hospital, 2150 Georgetown Road, Lexington, KY 40511; e-mail: smorrison@roodandriddle.com.

1. Introduction

Feet affected by chronic laminitis suffer from detachment of the dermal-epidermal interface and various patterns of pedal bone displacement.¹  Once separation of this interface occurs, horses heal with varying degrees of stability. Healing in the chronic laminitic foot is primarily through lamellar epidermal cell hyperplasia or lamellar wedge formation.^2,3  The lamellar wedge is composed of hyperplastic/dysplastic epidermal tissue with variation of tissue keratinization.³  The degree of stability is indirectly related to the thickness of the lamellar wedge.^4,5  That is, the more hyperplastic undifferentiated thickened tissue is less stable. This tissue is often referred to as “rubbery” and does not secure the pedal bone to the hoof wall and would be considered “unstable.” The more stable laminitic foot heals back with a tighter horn to pedal bone junction with less lamellar wedge formation. Factors which are believed to affect the degree of healing are: the extent of initial lamellar insult, subsequent structural damage, and the magnitude of distractive forces placed on the lamina. Reducing distractive forces by providing proper digital support (wedging heels, providing axial support, foot casts), and by reducing the load placed on the affected limbs (slings, weight displacement with water, recumbency) early in the course of the disease will likely contribute to the degree of healing.

In spite of the most aggressive treatment and management, many cases heal with inferior tissue quality and chronic instability. Unfortunately, it can take several months to realize the integrity of tissue that heals the damaged lamellar interface. The laminitic horse may spend months enduring painful rehabilitation, only to be euthanized because the quality of tissue regenerated is found to be inferior. These horses’ feet suffer frequent setbacks from sepsis and digital instability. This all too common scenario is extremely frustrating and costly to the owner. Mesenchymal stem cell (MSC) therapy has recently become an attractive treatment modality because of its potential to influence the quality of tissue that repairs a lesion. Mesenchymal stem cell therapy has been shown to improve the quality of healing in various orthopedic lesions.^6-12 To date, no studies have been completed to determine the effects MSC therapy may have on healing or improvement in success rates when used adjunctively to treat laminitic cases. Stem cell activity in a foot damaged by laminitis may play a role in the type of healing. Decreased stem cell expression has been observed in lamellar tissue samples from feet with chronic laminitis.¹³ Stem cell therapy has also been shown to have an anti-inflammatory effect¹⁴ and, therefore, may have a temporary palliative effect on chronic laminitic cases after treatment. This study looks at laminitic cases treated with mesenchymal stem cells as an adjunctive therapy between 2010 and 2013. Success rates are compared to previously published data in cases treated (without stem cell therapy) from our practice.^15,16

2. Materials and Methods

Case Selection

Cases with laminitis categorized as uncompensated/ unstable were selected to be treated with stem cell therapy. Uncompensated laminitis cases are defined as having severe damage to one or more of the growth centers (coronary corium or sole corium) of the foot. These cases have no evidence of sole and/or wall growth over time. In more acute cases, venograms show perfusion deficits, indicated by a lack of contrast material in the vasculature in weight bearing and unweighted images. Uncompensated cases often have shear lesion of the coronary band, seroma and abscess formation, and sometimes more serious deeper infections of the pedal bone.

Cases treated for chronic unstable laminitis were divided into 3 groups: acute rotation only (<30 days), sinkers, and chronic cases with advanced bone disease. Success rates for each category treated at the authors’ clinic have previously been published.^15,16 Records from cases with laminitis and adjunctive treatment with mesenchymal stem cells since August 2010 were evaluated. The cases treated with MSCs were classified according to the specific type of laminitis existing in each. Cases were placed into three categories: (1) severe rotation with mild to no bone disease, (2) chronic laminitis with significant bone disease, (3) sinking. Success rates were compared to the previously published data.

Stem cell therapy was performed either by retrograde venous digital perfusion or intra-arterial injection (Fig. 1) at the level of the palmar/plantar digital vein/artery. Each patient was sedated with detomidine. Perineural anesthesia was performed at the basisesamoid level with 2% mepivicaine hydrochloride. For intravenous perfusion, surgical tubing tourniquet was place around the metacarpal phalangeal joint. The medial or lateral palmar/plantar digital vein site was scrubbed and prepped. A 26-g 3⁄4 inch butterfly catheter is placed into the digital vein and the limb slowly perfused with a solution containing 20 to 30 million cells suspended in saline (Fig. 2). The foot was unweighted during at least half of the injection process. The tourniquet and perfusate was left in place for 25 to 30 minutes before removing the catheter and tourniquet. For intra-arterial injection, the medial or lateral palmar digital artery site was scrubbed and prepped. The palmar digital artery was palpated and isolated between the thumb and index finger. A 25-g 3⁄4 inch needle was inserted into the palmar digital artery in a proximal to distal direction, once in the artery a pulsating stream of arterial blood is seen from the needle. The syringe is gently attached to the needle hub, and the stem cell dose is slowly injected.
 

Treated limbs were then bandaged following the procedure. Each case received an allogenic umbilical cord blood derived mesenchymal cell dose as the first treatment. Bone marrow from the sternum was harvested, cultured, and expanded for subsequent treatments. All cases were treated at monthly intervals, and the average case received 3 to 4 treatments per affected foot.

3. Results

There is a relationship between time to first treatment and success.

The median time to first treatment was 71.5 days. For horses who were first treated sooner than 71.5 days, 87% (13/15) were successful. For horses whose first treatment was more than 71.5 days, 53% (8/15) were successful (P = 0.0464).

Although not quite statistically significant, age is also related to success. The median age of the horses was 11. [...]