TABLE 2.

Main characteristics of the 14 studies included in the review on bone marrow mesenchymal stem cells.

Studies		Species of cells			Sorts of cells			Recipient animal			In vitro/in vitro			Scaffold		Definition of auricular cartilage differentiation			Conclusion
Hassan et al. (2022)		Rabbit			ADSCs, BMSCs, ESCs a			Rabbit			In vivo			—		Histopathological examination (HE i , Masson, toluidine blue, and orcein) and immunohistology (S-100)			BMMSCs had the highest proliferation rate and chondrogenic potential compared to ADSCs and ESCs, as shown in histological assessments, with better reactivity of the S-100 protein and higher production of col II, aggrecan, and TGF-b1, which could be of superior value over ADSCs and ESCs for the regeneration of the cartilaginous defects
Cheng et al. (2014)		Rabbit			BMMSCs			Rabbit			In vivo			PLGA b		Histopathological examination (HE)			BMMSCs can be used as seed cells to repair cartilaginous defects in the head and neck through cartilage tissue engineering and shed light on the potential of the application of BMMSCs in clinical cartilage tissue engineering
Cohen et al. (2018)		Human			BMMSCs, ACCs c			Nude mouse/Rat			In vivo			Collagen hydrogel		Histopathological examination (Safranin O/Fast green, picrosirius red, and Verhoeff’s/Van Gieson)			The successful engineering of a patient-specific human auricle using exclusively human cell sources without extensive in vitro tissue culture prior to implantation, a critical step toward the clinical application of tissue engineering for auricular reconstruction
Dong et al. (2022)		Human			BMMSCs, ACCs			Nude mouse			In vivo			PLA d		Histopathological examination (HE, Safranin O/fast green, and Verhoeff’s/Van Gieson)			Co‐implantation of ACCs and BMMSCs a ratio as low as 1:9 of ACCs to BMMSCs within a Type I collagen matrix generates clinically relevant sized cartilage indistinguishable from that of native auricular cartilage upon gross, histologic, and biomechanical analysis after 6 months in vivo
Hou et al. (2022)		Rabbit			BMMSCs			Pig			In vivo			—		Histopathological examination (HE and Safranin O/fast green) and immunohistology (PRG4 and α-SMA)			The current study demonstrated that the in situ native cartilage niche is the determining factor for the ultimate regenerated cartilage type of stem cells and chondrocytes. It can regulate the directional differentiation of stem cells and transdifferentiation of chondrocytes to regenerate a specific type of cartilage consistent with the native niche
Kang et al. (2012)		Pig			BMMSCs, ACCs			Nude mouse			In vivo			PGA e /PLA		Histopathological examination (HE and Safranin O) and immunohistology (collagen type II, delta-like1/fetal antigen1, and Ki67)			The hypertrophy and mineralization of engineered cartilage in the approach of BMSC chondrogenic induction were found to be consistent with the upregulation of RUNX2 and downregulation of SOX9. Moreover, the approach of co-culturing BMMSCs and auricular chondrocytes reduced the hypertrophy, enhanced the elastic modulus, and improved the chondrogenic and proliferative potentials of engineered cartilage
Kang et al. (2013)		Pig			BMMSCs, ACs f			—			In vitro			PGA		Histopathological examination (HE and Safranin O) and immunohistology (collagen type II)			As few as 30% of chondrocytes could be used as seeding cells for the construction of cartilage with a satisfactory shape and quality when co-cultured with BMMSCs
Karimi et al. (2016)		Human			BMMSCs			Nude rat			In vivo			—		Histopathological examination (HE)			Using the ear cadaver framework seeded with bone marrow stem cells for reconstruction of ear is a feasible, fast, 1-stage technique and the elasticity, shape, size, and weight of the framework would be preserved
Morrison et al. (2016)		Calf			BMMSCs, ACCs			Nude mouse			In vivo			Collagen hydrogel		Histopathological examination (Safranin O/fast green and Verhoeff’s/Van Gieson)			We demonstrate a clinically translatable cell-sourcing strategy to fabricate elastic cartilage using only half the number of auricular chondrocytes normally required
Pleumeekers et al. (2015)		Calf, human			BMMSCs, ACCs			Nude mouse			In vivo			—		Immunohistology (collagen type II)			This study demonstrates that constructs containing a combination of 80 percent human bone marrow-derived mesenchymal stem cells and 20 percent bovine ear or nasal chondrocytes produced similar quantities of cartilage matrix components as constructs containing only chondrocytes
Posniak et al. (2022)		Human			BMMSCs, ACCs			—			In vitro			—		Histopathological examination (HE and toluidine blue)			These results showed that the combination of MSCs and ACCs can yield cell proliferation similar to that of MSC controls. Simultaneously, the combination of MSCs and ACCs produces chondrogenic expressions that match that of ACCs controls
Zhang et al. (2014)		Human, goat			BMMSCs, ACCs			Nude mouse			In vivo			PGA		Histopathological examination (HE and Safranin O) and immunohistology (collagen type II)			Regenerative technology of human-ear shaped cartilaginous tissue based on MCs and stem cells with lower cost and more stable cartilage formation was successfully established by the co-transplanting strategy, which provided a promising strategy for clinical translation of the engineered human-ear shaped cartilaginous tissue
Zhao et al. (2017)		Sheep			BMMSCs, ACCs			Nude mouse			In vivo			Collagen		Histopathological examination (HE, toluidine blue, and Safranin O) and immunohistology (collagen types I and II)			Chondrocyte-conditioned medium had a stronger influence on chondrogenesis than supplementation of the standard culture medium with TGF-β3 without inducing calcification
Otto et al. (2018)		Horse			BMMSCs, ACCs, PPCs g			—			In vitro			GelMA hydrogel		Histopathological examination (HE and Safranin O/fast green) and immunohistology (collagen types I, II, and VI)			Although under the current culturing conditions, bone marrow derived MSCs seemed to perform better in terms of matrix production, major advantages of ACPCs h include the ability to generate high cell numbers, upregulation of the elastin gene, and a limited endochondral ossification potential

^a ESCs, ear stem cells.

^b PLGA, poly (dl-lactide-co-glycolide).

^c ACCs, auricular cartilage cells.

^d PLA, polylactic acid.

^e PGA, polyglycolic acid.

^f ACs, articular cartilage cells.

^g PPCs, perichondrial progenitor cells.

^h ACPCs, auricular cartilage progenitor cells.

ⁱ HE, hematoxylin and eosin.