Cell-Based Therapies for the Treatment of Shoulder and Elbow Tendinopathies: A Scoping Review

Table 2

Synopsis of clinical studies dealing with cell-based approaches in elbow tendon pathology.

Publication	Level of evidence	Modified Coleman score	Pathology	of patients	Therapeutic protocol	MSC manipulation	Outcomes and imaging	Follow-up	Results
Moon et al., Ann Acad Med Singapore [25]	IV case series	48	Medial and/or lateral epicondylitis	24 (26 elbows)	Arthroscopic from anterior Iliac crest	20 ml of bone marrow plasma was centrifuged and kept in the refrigerator. Only the clear upper layer and the buffy coat layer were used obtaining 8 to 9 ml mixed with 3 ml of bupivacaine before injection	VAS,	8 weeks and 6 months	(i) Statistically significant improvement in VAS and MEPS; (ii) No complications, 2 failures; (iii) Healthy tendon appearance at US at 6 months
Connell et al., Br J Sports Med [28]	IV case series (pilot study)	45	Lateral epicondylitis	12	Injection of collagen-producing cells from dermal fibroblasts	4 mm skin sample obtained from the lateral side of the hip. Lab preparation of the cells and injections of collagen-producing cells (approximately 2 ml)		6 weeks, 3 weeks, and 6 months	(i) Statistically significant improvement in PRTEE; (ii) No complications, 1 failure; (iii) Healthier tendon appearance at US in terms of tendon thickness, hypoechogenicity, intrasubstance tears, and neovascularity at 6 months
Wang et al., AJSM [30]	IV case series	47	Lateral epicondylitis	18	Injections of expanded autologous tenocytes from patellar tendon	A strip of tendon was harvested from the superficial surface of the patellar tendon. Tenocytes were cultivated and up to 2 ml of autologous tenocytes ( cells/ml) suspended with 10% autologous human serum were injected after 3 weeks	VAS, qDASH, grip strength, +MRI score (12 months)	1, 2, 3, 12, 12 months	(i) Statistically significant improvement in VAS score, qDASH, grip strength score, and MRI scores after surgery and at last follow-up; (ii) No major complications at donor or injection site; (iii) 2 patients withdrew and had surgery
Singh et al., J Nat Sci Biol Med [26]	IV case series	45	Lateral epicondylitis	30	BMAC from iliac crest	10 ml of bone marrow plasma was centrifuged; only the clear upper layer and the buffy coat layer was used obtaining 4 to 5 ml mixed with 1 ml of 2% lignocaine solution before injection	PRTEE	2 weeks, 6 weeks, and 3 months	(i) Statistically significant improvement in PRTTE; (ii) No major complications
Lee et al., Stem Cells [27]	IV case series	49	Lateral epicondylitis	12	allo-adMSC mixed with fibrin glue injection	Lipoaspirates of human subcutaneous fat tissue obtained from healthy donors were treated in the lab obtaining allo-a-dMSC. All the procedures followed the “Cell Bank process”. Injections of 0.5 ml thrombin mixed with 10^6 or 10^7 (2 doses) of allo-ASCs in the first syringe and 0.5 ml fibrinogen in the other syringe	MEPI,	2 weeks, 6 weeks, 12 weeks, and 52 weeks	(i) VAS and MEPI score significantly improved and tendon defect decreased at US over the course of the follow-up; (ii) No significant adverse effects; (iii) No significant differences between the two dose groups, even if faster pain improvement and earlier plateauing of performance scores were observed in the higher dose group
Wang et al., AJSM [30]	IV case series	52	Lateral epicondylitis	15	Injections of expanded autologous tenocytes from patellar tendon	As above	VAS, qDASH, UEFS, grip score	4 years, 5 years	(i) Significant improvements from preop were maintained in all clinical and MRI scores for up to 5 years after treatment; (ii) At final follow-up, 93% of patients were either highly satisfied or satisfied; 1 patient (with tear progression) was not satisfied

BMAC: bone marrow aspirate concentrate; allo-adMSC: allogeneic adipose-derived mesenchymal stem cells; MEPS: Mayo Elbow Performance Scoring; PRTEE: Patient-Rated Tennis Elbow Evaluation; qDASH: Quick Disability of the Arm, Shoulder, Hand Score; VAS: visual analog scale; UEFS: upper extremity functional scale; MRI: magnetic resonance imaging; US: ultrasound.