Adipose-derived stem cell therapy shows promising results for secondary lymphedema

Table 1 Adipose-derived stem cell-based therapy for secondary lymphedema in animals

Year	Ref.	Animal number	Edema site	Lymphoedema modeling	ADSC origin	Cell dose	Injection method	Auxiliary treatment	Valuation criteria	Result(s)
2011	Hwang et al[43]	n = 5 (5 groups)	Hindlimb	Circumferential incision	Human	NM	Injected subcutaneously at the site of the damaged lymphatic vessels	VEGF-C hydrogel (A VEGF-C hydrogel sheet was applied to the injection site and was sutured into the injured dermal junction)	(1) Circumference; and (2) IHC staining (LYVE-1, PKH-26)	(1) A significant decrease in dermal edema at 3-4 wk; and (2) Significant lymphatic vessel regeneration
2012	Shimizu et al[44]	n = 12 (3 groups)	Tail	Circumferential incision	Allogeneic	2 × 106	Injected at two different points of the lymphedematous skin flap	N	Circumference	A decrease in lymphedema
2015	Ackermann et al[45]	n = 10 (3 groups)	Tail	Circumferential incision	Allogeneic	NM	NM	N	(1) Circumference; (2) IHC staining (LYV-1); and (3) Real-time laser Doppler imaging for wound perfusion	(1) ADSCs affected lymphangiogenesis and lymphedema development; and (2) PRP affected more significantly than ADSCs
2015	Yoshida et al[42]	n = 20 (5 groups)	Hindlimb	Circumferential incision	Allogeneic	1 × 104; 1 × 15; 1 × 106	NM	N	(1) Circumference; and (2) IHC (LYVE, VEGF-C,VEGFR, EGFP)	The number of lymphatic vessels significantly increased at 2 wk, which was dose-dependent of implanted ADSCs
2017	Hayashida et al[41]	n = 5 (4 groups)	Hindlimb	Circumferential incision	Allogeneic	1 × 106	Injected subcutaneously at proximal and distal limb	N	(1) Hind-paw edema volume; and (2) IHC (LYVE-1, VEGF-C)	Increased the number of lymphatic vessels; induced the lymphatic flow drainage to the circulatory system

ADSCs: Adipose-derived stem cells; IHC: Immunohistochemistry; LYVE-1: Lymphatic vascular hyaluronan receptor-1; Prox-1: Prospero homeobox protein 1; PRP: Platelet-rich plasma; VEGF: Vascular endothelial growth factor; VEGFR: Vascular endothelial growth factor receptor; NM: Not mentioned; N: None.

Table 2 Adipose-derived stem cells-based therapy for secondary lymphedema in human

Year	Ref.	Study type	Patient number	Edema site	Etiology	ADSC origin	Cell dose	Injection method	Auxiliary treatment	Valuation criteria	Result(s)	Follow-up
2015	Peña Quián et al[46]	Case report	1	Lower limb	Recurrent lymphangitis	Autologous	1-2.2 × 109	NM	N	Lymphoscintigraphy	The presence of new lymphatic ramifications and a greater number of lymph nodes	6 mo
2016	Toyserkani et al[47]	Nonramdomized clinical trial	1	Upper limb	BCRL	Autologous	4.07 × 107	Injected at 8 different points of axilla	Fat grafting (10 mL)	(1) Circumference; (2) DXA scans; and (3) Discomfort (infection, pain, and swelling)	(1) A reduction in volume; (2) Relief of symptoms (heaviness and tension); (3) A reduction of compression therapy; and (4) No complication	1 and 4 mo
2017	Toyserkanl et al[48]	Nonramdomized clinical trial	10	Upper limb	BCRL	Autologous	5 × 107	Injected at 8 different points of axilla	Fat grafting (28 mL)	(1) Volume assessment; (2) DXA scans; and (3) Discomfort (redness, swelling, itching, pain, and infection)	No significant reduction in volume; reduction of conservative managements (50%); reduction of symptoms	1, 3, 6, and 12 mo
2019	Toyserkanl et al[49]	Nonramdomized clinical trial	10	Upper limb	BCRL	Autologous	5 × 107	Injected at 8 different points of axilla	Fat grafting (30 mL)	(1)Volume assessment; (2) DXA scans; and (3) Discomfort (redness, swelling, itching, pain, and infection)	No significant reduction in volume; reduction of conservative managements (50%)	1, 3, 6, and 12 mo

ADSCs: Adipose-derived stem cells; BCRL: Breast cancer–related lymphedema; NM: Not mentioned; N: None.