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. 2023 Feb 14;14(2):104.
doi: 10.3390/jfb14020104.

A Novel Dressing Composed of Adipose Stem Cells and Decellularized Wharton's Jelly Facilitated Wound Healing and Relieved Lymphedema by Enhancing Angiogenesis and Lymphangiogenesis in a Rat Model

Jen-Her Lu  1   2 , Kai Hsia  3   4 , Chih-Kuan Su  4 , Yi-Hsiang Pan  4 , Hsu Ma  4   5 , Shih-Hwa Chiou  3   6 , Chih-Hsun Lin  4   5
Affiliations

A Novel Dressing Composed of Adipose Stem Cells and Decellularized Wharton's Jelly Facilitated Wound Healing and Relieved Lymphedema by Enhancing Angiogenesis and Lymphangiogenesis in a Rat Model

Jen-Her Lu et al. J Funct Biomater. .

Abstract

Lymphedema causes tissue swelling due to the accumulation of lymphatic fluid in the tissue, which delays the process of wound-healing. Developing effective treatment options of lymphedema is still an urgent issue. In this study, we aim to fabricate tissue-engineered moist wound dressings with adipose stem cells (ASCs) and decellularized Wharton's jelly (dWJ) from the human umbilical cord in order to ameliorate lymphedema. Rat ASCs were proliferated and an apparent layer was observed on dWJ at day 7 and 14. A rat tail lymphedema model was developed to evaluate the efficacy of the treatment. Approximately 1 cm of skin near the base of the rat tail was circularly excised. The wounds were treated by secondary healing (control) (n = 5), decellularized Wharton's jelly (n = 5) and ASC-seeded dWJ (n = 5). The wound-healing rate and the tail volume were recorded once a week from week one to week five. Angiogenesis and lymphangiogenesis were assessed by immunochemistry staining with anti-CD31 and anti-LYVE1. The results showed that the wound-healing rate was faster and the tail volume was lesser in the ASC-seeded dWJ group than in the control group. More CD31+ and LYVE-1+ cells were observed at the wound-healing area in the ASC-seeded dWJ group than in the control group. This proves that tissue-engineered moist wound dressings can accelerate wound-healing and reduce lymphedema by promoting angiogenesis and lymphangiogenesis.

Keywords: angiogenesis; decellularized Wharton’s jelly; lymphangiogenesis; lymphedema; rat adipose stem cell; wound-healing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Rat tail lymphedema model and decellularized Wharton’s jelly from human umbilical cord. (A) rat tail before operation demonstrating the wound position and size; (B) rat tail after operation showed the lymphedema distal to the wound; (C) calculation of rat tail volume; (D) gross view of the decellularized Wharton’s jelly; (E) HE staining of Wharton’s jelly from human umbilical cord; (F) HE staining of decellularized Wharton’s jelly from human umbilical cord. The figure shows that the cells were eliminated from the Wharton’s jelly. Magnification 200×; scale bar = 5 μm.
Figure 2
Figure 2
Rat ASC. (A) in vitro characterization of ASC markers at passage 7 to 10. The image and characterization of ASCs by FACS; (B) the chondrogenic differentiation of ASC by Alcian Blue staing; (C) the osteogenic differentiation of ASC by Alizarin Red staining; (D) the adipogenic differentiation of ASC by Oil Red O staining; (E) the proliferation curve of ASCs on the Petri dish and dWJ; (F) DAPI and HE staining of ASC-dWSJ after cells were seeded for 7 days and 14 days. Magnification 200×; scale bar = 5 μm. * p < 0.05, **** p < 0.001.
Figure 3
Figure 3
Images of rat tail lymphedema and wound-healing after dWJ and rASC/dWJ treatment for five weeks after injury. (A) images of rat tails of control group from week 0 to week 5; (B) images of rat tails of dWJ group from week 0 to week 5; (C) images of rat tails of dWJ group from week 0 to week 5. Photographs of week 0 represent the mouse tails treated without and with dressings just after surgical excision and the wound width for each group was made as similar as possible. During wound development, the lymphedema of control group was the most significant compared with the two treatment groups. The wound widths of rASC/dWJ groups seem smaller than the other two groups from week one to five after treatment. n = 5/group.
Figure 4
Figure 4
Evaluation of lymphedema and wound-healing after treatment with dWJ and rASC/dWJ for 5 weeks. (A) increase in lymphedema was assessed by tail volume for each week compared with pre-operational tail volume; (B) wound width. * p < 0.05.
Figure 5
Figure 5
The angio-expression of CD31 and LYVE-1 in the excision sites after five weeks. Immunohistochemistry of (A) control group; (B) dWJ group; (C) rASC/dWJ group. The results showed that although both CD31 and LYVE-1 positive cells in treating groups (rASC/dWJ group and dWJ group) were more than in the control group, the rASC/dWJ group contained the most positive cells among these three groups. The red arrows point to capillary blood vessels and the green arrows to lymphatic vessels. Magnification of 40×, scale bar = 200 μm; magnification of 400×, scale bar =20 μm. (D) The qualification of CD31 positive cells; (E) the qualification of LYVE-1 positive cells. The statistical data demonstrate that both CD31 and LYVE-1 positive cells in rASC/dWJ group were significantly more than the control and dWJ group. * p < 0.05.
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